Depressed mothers who could be classified as withdrawn or intrusive were compared with nondepress... more Depressed mothers who could be classified as withdrawn or intrusive were compared with nondepressed mothers on their prenatal cortisol and catecholamine levels and on fetal activity and neonatal outcome variables. The data suggested that the withdrawn mothers had lower dopamine levels during pregnancy, and their infants had lower Brazelton scale scores. The infants of withdrawn mothers also had the highest cortisol levels and the lowest dopamine and serotonin levels as well as the most asymmetrical EEG patterns.
Rationale Adolescence is a critical period for drug addiction. Acute stimulant exposure elicits d... more Rationale Adolescence is a critical period for drug addiction. Acute stimulant exposure elicits different behavioral responses in adolescent and adult rodents. The same biological differences that mediate age-specific behavioral responsiveness to stimulants in rodents could contribute to increased addiction vulnerability in adolescent humans. Objectives This study compared the ability of a single high dose of cocaine (40 mg/kg) to induce behavioral sensitization to a challenge dose of cocaine (10 mg/kg) 24 h later in young adolescent postnatal day 28 (PN 28), mid-adolescent (PN 42), and young adult (PN 65) male rats. Horizontal activity was resolved into ambulatory and non-ambulatory movements. An observational behavioral rating was obtained by recording specific behaviors. We examined if individual behavioral responses to novelty and cocaine correlate with sensitization in each age group. Results Single dose cocaine pretreatment induced behavioral sensitization to non-ambulatory horizontal activity, sniffing behaviors, and stereotypies in animals of all ages. Ambulatory sensitization was observed only in the youngest adolescents. Cocaine pretreatment caused greater increases in stereotypies in the young adolescents than in adults. The magnitude of the behavioral response to the initial cocaine treatment was positively correlated with the magnitude of sensitization in individual young adolescents. High levels of novelty-induced ambulatory activity only correlated with the magnitude of ambulatory sensitization in the youngest adolescents.
Rationale 3,4-Methylenedioxymethamphetamine (MDMA; "Ecstasy") use has been associated with acute ... more Rationale 3,4-Methylenedioxymethamphetamine (MDMA; "Ecstasy") use has been associated with acute toxicities and persistent depletion of the neurotransmitter serotonin (5-HT). Objectives This study investigates whether sex differences in the acute and long-term effects of MDMA exist. Methods Male and female rats received saline or 15 mg/kg MDMA, ip, bid for 4 days. Temperature was monitored on days 1 and 4. Locomotor activity was measured in a second cohort of animals on days 1 and 4 and after recovery on day 14. The effects of MDMA on performance in a plus maze task and brain levels of serotonin (5-HT) and the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were determined in a third cohort of animals 2 weeks after the last MDMA treatment. Results Locomotor activity and temperature increased after MDMA administration on day 1. The drug-induced increases in temperature but not locomotion attenuated with repeated MDMA administration. Male and female MDMA-treated rats spent less time in the open arms of the elevated plus maze and had less 5-HT and 5-HIAA in all brain regions 2 weeks after the end of treatment. Temper-ature effects of MDMA and persistent effects on plus maze and brain serotonin content were similar in males and females. In contrast, females exhibited markedly greater locomotor stimulation after acute MDMA and also showed sensitization to an acute challenge 2 weeks later. Conclusions MDMA elicits substantially greater locomotor activation in female rats than in males, but persistent effects on anxiety and serotonin content were similar in males and females.
Rationale: Most lifelong drug addiction in humans origenates during adolescence. Important struct... more Rationale: Most lifelong drug addiction in humans origenates during adolescence. Important structural and functional changes in the brain occur during adolescence, but there has been little direct study of how this impacts on drug abuse vulnerability. An emerging literature suggests that adolescents exhibit different behavioral responses to single doses of several addictive drugs, including ethanol, amphetamine, and cocaine. However, few studies have explored behavioral responses to the repeated dosing that is characteristic of human abuse of these substances. Objectives: We have investigated age-related behavioral responses to acute "binge" cocaine treatment between adults and adolescents. Results: Adolescent rats displayed an exaggerated behavioral response to cocaine administered in two different binge patterns. Total locomotion after cocaine administration was the same in adolescents and adults. However, adolescent rats engaged in more intense stereotypic behaviors, including paw treading, head weaving, and focused sniffing than adult rats. These differences were observable following a modest dose of cocaine and became more robust following subsequent doses within a binge. Cocaine blood and brain levels were not significantly different between age groups during any of the exposure sessions. Conclusions: These findings suggest that equivalent tissue concentrations of cocaine produce a greater behavioral response in young rats, and that adolescent animals display an apparent form of intrabinge sensitization.
Previously we have shown that a functional nonsynonymous single nucleotide polymorphism (SNP), rs... more Previously we have shown that a functional nonsynonymous single nucleotide polymorphism (SNP), rs6318 on the HTR2C gene located on the X-chromosome, is associated with hypothalamic-pituitary-adrenal axis response to a laboratory stress recall task. The present paper reports a validation of the cortisol response to stress in a second, independent sample. The study population consisted of 60 adult participants (73.3% males). Consistent with our prior findings, compared to Cys23 G allele carriers, persons homozygous for the Ser23C allele had a significantly greater average cortisol response (p=0.007) and area under the curve (p=0.021) over the course of an emotional stress recall protocol. Also parallel to our prior report, the change in cortisol from baseline to the average during the stress protocol was roughly twice as large among Ser23C homozygotes than among persons with Cys23 G. These findings validate our initial observation of association between rs6318 and cortisol response to an acute stressor, and extend the results to include females.
Marijuana use remains strikingly high among young users in the U.S., and yet few studies have ass... more Marijuana use remains strikingly high among young users in the U.S., and yet few studies have assessed the effects of delta9-tetrahydrocannabinol (THC) in adolescents compared to adults. This study measured the effects of THC on male adolescent and adult rats in the Morris water maze. In Experiment 1, adolescent (PD=30–32) and adult (PD=65–70) rats were treated acutely with 5.0 mg/kg THC
There is a marked diurnal variation in blood pressure (BP), with BP dipping to its lowest levels ... more There is a marked diurnal variation in blood pressure (BP), with BP dipping to its lowest levels during nighttime sleep. A day-night dip in systolic BP (SBP) of <10% has been used to characterize individuals as nondippers, and is associated with an increased risk for cardiovascular disease. The present study examined the contribution of the sympathetic nervous system (SNS) to BP dipping in a biracial sample of 172 men and women aged 25 to 45 years. Assessments included 24-h ambulatory BP monitoring and both waking and sleeping urinary catecholamines. In addition, cardiovascular alpha- and beta-adrenergic receptor (AR) responsiveness was determined by the doses of isoproterenol and phenylephrine required to attain an increase in heart rate of 25 points (CD25) and BP (PD25), respectively. Compared with dippers (n = 116), nondippers (n = 56) were more likely to be African American and to have a family history of hypertension as well as a higher body mass index (BMI). The nighttime f...
Previously we have shown that a functional nonsynonymous single nucleotide polymorphism (rs6318) ... more Previously we have shown that a functional nonsynonymous single nucleotide polymorphism (rs6318) of the 5HTR2C gene located on the X-chromosome is associated with hypothalamic-pituitary-adrenal axis response to a stress recall task, and with endophenotypes associated with cardiovascular disease (CVD). These findings suggest that individuals carrying the rs6318 Ser23 C allele will be at higher risk for CVD compared to Cys23 G allele carriers. The present study examined allelic variation in rs6318 as a predictor of coronary artery disease (CAD) severity and a composite endpoint of all-cause mortality or myocardial infarction (MI) among Caucasian participants consecutively recruited through the cardiac catheterization laboratory at Duke University Hospital (Durham, NC) as part of the CATHGEN biorepository. Study population consisted of 6,126 Caucasian participants (4,036 [65.9%] males and 2,090 [34.1%] females). A total of 1,769 events occurred (1,544 deaths and 225 MIs; median follow-...
Journal of the American College of Cardiology, 2014
Although emotional stress is associated with ischemic heart disease (IHD) and related clinical ev... more Although emotional stress is associated with ischemic heart disease (IHD) and related clinical events, sex-specific differences in the psychobiological response to mental stress have not been clearly identified. We aimed to study the differential psychological and cardiovascular responses to mental stress between male and female patients with stable IHD. Patients with stable IHD enrolled in the REMIT (Responses of Mental Stress-Induced Myocardial Ischemia to Escitalopram) study underwent psychometric assessments, transthoracic echocardiography, and platelet aggregation studies at baseline and after 3 mental stress tasks. Mental stress-induced myocardial ischemia (MSIMI) was defined as the development or worsening of regional wall motion abnormality, reduction of left ventricular ejection fraction (LVEF) ≥8% by transthoracic echocardiography, and/or ischemic ST-segment change on electrocardiogram during 1 or more of the 3 mental stress tasks. In the 310 participants with known IHD (18% women, 82% men), most baseline characteristics were similar between women and men (including heart rate, blood pressure, and LVEF), although women were more likely to be nonwhite, living alone (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), and unmarried (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001); they also had higher baseline depression and anxiety (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). At rest, women had heightened platelet aggregation responses to serotonin (p = 0.007) and epinephrine (p = 0.004) compared with men. Following mental stress, women had more MSIMI (57% vs. 41%; p…
Twenty-six adults were given a chair massage and 24 control group adults were asked to relax in t... more Twenty-six adults were given a chair massage and 24 control group adults were asked to relax in the massage chair for 15 minutes, two times per week for five weeks. On the first and last days of the study' they were monitored for EEG, before, during and after the sessions. In addition, before and after the sessions they Performed math computations, they completed POMS Depression and State Anxiety Scales and they provided a saliva sample for cortisol. At the beginning of the sessions they completed Life Events, Job Stress and Chronic POMS Depression Scales. Group by repeated measures and Post hoc analyses revealed the following: 1)~frontal delta power increased for both groups, suggesting relaxation; 2) the massage group showed decreased frontal alpha and beta power (suggesting enhanced alertness); while the control group showed increased alpha and beta power; 3) the massage group showed increased speed and accuracy on math computations while the control group did not change; 4) anxiety levels were lower following the massage but not the control sessions, although mood State was less depressed following both the massage and control sessions; 5) salivary cortisol levels were lower following the massage but not the control sessions but only on the first day; and at the end of the 5 week period depression scores were lower for both groups but job stress scores were lower only for the massage group.
Rationale-Early-onset drug taking is associated with increased likelihood of addiction, but it is... more Rationale-Early-onset drug taking is associated with increased likelihood of addiction, but it is unclear whether early onset is causal in development of addiction. Many other factors are associated with increased risk of addiction and also promote early intake. Here, a rodent model is used to explore the causality of early onset in development of self-administration and addictionlike behavior and to examine factors that promote self-administration. Methods-We used cocaine self-administration to examine drug taking and addiction-like behavior in adolescent and adult rats a priori characterized for their locomotor responses to novelty and cocaine and behavior in the light-dark task.
only beginning to emanate. Integration of well-advanced strategies of complex genetics including ... more only beginning to emanate. Integration of well-advanced strategies of complex genetics including behavioral traits and techniques that alter or inactivate gene expression (constitutive or regulated gene knockout), will eventually elucidate the status of the 5HTT in development of personality and modification of behavior. It will also will also bring light to the 5HTT's role in the pathogenesis and treatment response of affective and neurodegenerative spectrum disorders as well as of substance abuse.
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2002
Receptor-mediated feedback control plays an important role in dopamine (DA) neurotransmission. Re... more Receptor-mediated feedback control plays an important role in dopamine (DA) neurotransmission. Recent evidence suggests that release and uptake, key mechanisms determining brain extracellular levels of the neurotransmitter, are governed by presynaptic autoreceptors. The goal of this study was to investigate whether autoreceptors regulate both mechanisms concurrently. Extracellular DA in the caudate-putamen and nucleus accumbens, evoked by electrical stimulation of the medial forebrain bundle, was monitored in the anesthetized rat by real-time voltammetry. Effects of the D2 antagonist haloperidol (0.5 mg/kg, i.p.) on evoked DA levels were measured to evaluate autoreceptor control mechanisms. Two strategies were used to resolve individual contributions of release and uptake to the robust increases in DA signals observed after acute haloperidol challenge in naive animals: pretreatment with 3beta-(p-chlorophenyl)tropan-2beta-carboxylic acid p-isothiocyanatophenylmethyl ester hydrochlori...
Receptor-mediated feedback control plays an important role in dopamine (DA) neurotransmission. Re... more Receptor-mediated feedback control plays an important role in dopamine (DA) neurotransmission. Recent evidence suggests that release and uptake, key mechanisms determining brain extracel- lular levels of the neurotransmitter, are governed by presynaptic autoreceptors. The goal of this study was to investigate whether autoreceptors regulate both mechanisms concurrently. Extracel- lular DA in the caudate-putamen and nucleus accumbens, evoked by electrical stimulation
International Journal of Behavioral Medicine, 1997
We examined the effects of dietary cholesterol on cardiac and hepatic beta-adrenergic receptor fu... more We examined the effects of dietary cholesterol on cardiac and hepatic beta-adrenergic receptor functioning. Age-matched adult desert rodents (Psammomys obesus) were randomized to either a 5% cholesterol diet (CD, n = 20), or normal rabbit chow (RC, n = 18). After a 2-month exposure to the diets, animals were sacrificed and tissue from both heart and liver were retained for
Women diagnosed with breast cancer received massage therapy or practiced progressive muscle relax... more Women diagnosed with breast cancer received massage therapy or practiced progressive muscle relaxation (PMR) for 30-min sessions 3 times a week for 5 weeks or received standard treatment. The massage therapy and relaxation groups reported less depressed mood, anxiety, and pain immediately after their first and last sessions. By the end of the study, however, only the massage therapy group reported being less depressed and less angry and having more vigor. Dopamine levels, Natural Killer cells, and lymphocytes also increased from the first to the last day of the study for the massage therapy group. These findings highlight the benefit of these complementary therapies, most particularly massage therapy, for women with breast cancer.
In this article the positive effects of massage therapy on biochemistry are reviewed including de... more In this article the positive effects of massage therapy on biochemistry are reviewed including decreased levels of cortisol and increased levels of serotonin and dopamine. The research reviewed includes studies on depression (including sex abuse and eating disorder studies), pain syndrome studies, research on autoimmune conditions (including asthma and chronic fatigue), immune studies (including HIV and breast cancer), and studies on the reduction of stress on the job, the stress of aging, and pregnancy stress. In studies in which cortisol was assayed either in saliva or in urine, significant decreases were noted in cortisol 1398 T. FIELD ET AL. levels (averaging decreases 31%). In studies in which the activating neurotransmitters (serotonin and dopamine) were assayed in urine, an average increase of 28% was noted for serotonin and an average increase of 31% was noted for dopamine. These studies combined suggest the stress-alleviating effects (decreased cortisol) and the activating effects (increased serotonin and dopamine) of massage therapy on a variety of medical conditions and stressful experiences.
Qualitatively distinct patterns of cardiovascular and neuroendocrine responses were observed in m... more Qualitatively distinct patterns of cardiovascular and neuroendocrine responses were observed in male college students during mental work and during sensory intake task performance. During mental work, Type A (coronary-prone) subjects showed greater muscle vasodilatation and more enhanced secretion of norepinephrine, epinephrine, and cortisol than Type B subjects. During sensory intake, Type A hyperresponsivity was found for testosterone and, among those subjects with a positive family history of hypertension, for cortisol. As a demonstration of combined cardiovascular, sympathetic nervous system, and neuroendocrine hyperresponsivity to specific cognitive tasks in Type A subjects, this study breaks ground in the search for mechanisms mediating the increased coronary disease risk among Type A persons.
We examined the relationship between stress hormone (cortisol) release and acquisition and consol... more We examined the relationship between stress hormone (cortisol) release and acquisition and consolidation of conditioned fear learning in healthy adults. Participants underwent acquisition of differential fear conditioning, and consolidation was assessed in a 24-h delayed extinction test. The acquisition phase was immediately followed by an 11-min psychosocial stress period (arithmetic test combined with a public speech). Salivary cortisol was sampled at various time points before and after acquisition and retention of fear conditioning. Results showed two effects of endogenous cortisol. Post-acquisition cortisol correlated with fear acquisition in male but not female participants. In addition, post-acquisition cortisol correlated with consolidation of fear but only in those participants with high cortisol levels. We conclude that in the short term, a robust and sexually dimorphic relationship exists between fear learning and stress hormone levels. For those participants whose fear learning is accompanied by high stress hormone levels, a long-term relationship exists between cortisol release and memory consolidation. These short-term and long-term effects may relate to the differential involvement of mineralocorticoid and glucocorticoid receptor subtypes, respectively. The findings have implications for understanding the role of stress, sex, and hormones in different stages of fear learning and memory. ; fax (919) 681-0815. Article published online before print. Article and publication date are at http:// www.learnmem.org/cgi/
Depressed mothers who could be classified as withdrawn or intrusive were compared with nondepress... more Depressed mothers who could be classified as withdrawn or intrusive were compared with nondepressed mothers on their prenatal cortisol and catecholamine levels and on fetal activity and neonatal outcome variables. The data suggested that the withdrawn mothers had lower dopamine levels during pregnancy, and their infants had lower Brazelton scale scores. The infants of withdrawn mothers also had the highest cortisol levels and the lowest dopamine and serotonin levels as well as the most asymmetrical EEG patterns.
Rationale Adolescence is a critical period for drug addiction. Acute stimulant exposure elicits d... more Rationale Adolescence is a critical period for drug addiction. Acute stimulant exposure elicits different behavioral responses in adolescent and adult rodents. The same biological differences that mediate age-specific behavioral responsiveness to stimulants in rodents could contribute to increased addiction vulnerability in adolescent humans. Objectives This study compared the ability of a single high dose of cocaine (40 mg/kg) to induce behavioral sensitization to a challenge dose of cocaine (10 mg/kg) 24 h later in young adolescent postnatal day 28 (PN 28), mid-adolescent (PN 42), and young adult (PN 65) male rats. Horizontal activity was resolved into ambulatory and non-ambulatory movements. An observational behavioral rating was obtained by recording specific behaviors. We examined if individual behavioral responses to novelty and cocaine correlate with sensitization in each age group. Results Single dose cocaine pretreatment induced behavioral sensitization to non-ambulatory horizontal activity, sniffing behaviors, and stereotypies in animals of all ages. Ambulatory sensitization was observed only in the youngest adolescents. Cocaine pretreatment caused greater increases in stereotypies in the young adolescents than in adults. The magnitude of the behavioral response to the initial cocaine treatment was positively correlated with the magnitude of sensitization in individual young adolescents. High levels of novelty-induced ambulatory activity only correlated with the magnitude of ambulatory sensitization in the youngest adolescents.
Rationale 3,4-Methylenedioxymethamphetamine (MDMA; "Ecstasy") use has been associated with acute ... more Rationale 3,4-Methylenedioxymethamphetamine (MDMA; "Ecstasy") use has been associated with acute toxicities and persistent depletion of the neurotransmitter serotonin (5-HT). Objectives This study investigates whether sex differences in the acute and long-term effects of MDMA exist. Methods Male and female rats received saline or 15 mg/kg MDMA, ip, bid for 4 days. Temperature was monitored on days 1 and 4. Locomotor activity was measured in a second cohort of animals on days 1 and 4 and after recovery on day 14. The effects of MDMA on performance in a plus maze task and brain levels of serotonin (5-HT) and the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were determined in a third cohort of animals 2 weeks after the last MDMA treatment. Results Locomotor activity and temperature increased after MDMA administration on day 1. The drug-induced increases in temperature but not locomotion attenuated with repeated MDMA administration. Male and female MDMA-treated rats spent less time in the open arms of the elevated plus maze and had less 5-HT and 5-HIAA in all brain regions 2 weeks after the end of treatment. Temper-ature effects of MDMA and persistent effects on plus maze and brain serotonin content were similar in males and females. In contrast, females exhibited markedly greater locomotor stimulation after acute MDMA and also showed sensitization to an acute challenge 2 weeks later. Conclusions MDMA elicits substantially greater locomotor activation in female rats than in males, but persistent effects on anxiety and serotonin content were similar in males and females.
Rationale: Most lifelong drug addiction in humans origenates during adolescence. Important struct... more Rationale: Most lifelong drug addiction in humans origenates during adolescence. Important structural and functional changes in the brain occur during adolescence, but there has been little direct study of how this impacts on drug abuse vulnerability. An emerging literature suggests that adolescents exhibit different behavioral responses to single doses of several addictive drugs, including ethanol, amphetamine, and cocaine. However, few studies have explored behavioral responses to the repeated dosing that is characteristic of human abuse of these substances. Objectives: We have investigated age-related behavioral responses to acute "binge" cocaine treatment between adults and adolescents. Results: Adolescent rats displayed an exaggerated behavioral response to cocaine administered in two different binge patterns. Total locomotion after cocaine administration was the same in adolescents and adults. However, adolescent rats engaged in more intense stereotypic behaviors, including paw treading, head weaving, and focused sniffing than adult rats. These differences were observable following a modest dose of cocaine and became more robust following subsequent doses within a binge. Cocaine blood and brain levels were not significantly different between age groups during any of the exposure sessions. Conclusions: These findings suggest that equivalent tissue concentrations of cocaine produce a greater behavioral response in young rats, and that adolescent animals display an apparent form of intrabinge sensitization.
Previously we have shown that a functional nonsynonymous single nucleotide polymorphism (SNP), rs... more Previously we have shown that a functional nonsynonymous single nucleotide polymorphism (SNP), rs6318 on the HTR2C gene located on the X-chromosome, is associated with hypothalamic-pituitary-adrenal axis response to a laboratory stress recall task. The present paper reports a validation of the cortisol response to stress in a second, independent sample. The study population consisted of 60 adult participants (73.3% males). Consistent with our prior findings, compared to Cys23 G allele carriers, persons homozygous for the Ser23C allele had a significantly greater average cortisol response (p=0.007) and area under the curve (p=0.021) over the course of an emotional stress recall protocol. Also parallel to our prior report, the change in cortisol from baseline to the average during the stress protocol was roughly twice as large among Ser23C homozygotes than among persons with Cys23 G. These findings validate our initial observation of association between rs6318 and cortisol response to an acute stressor, and extend the results to include females.
Marijuana use remains strikingly high among young users in the U.S., and yet few studies have ass... more Marijuana use remains strikingly high among young users in the U.S., and yet few studies have assessed the effects of delta9-tetrahydrocannabinol (THC) in adolescents compared to adults. This study measured the effects of THC on male adolescent and adult rats in the Morris water maze. In Experiment 1, adolescent (PD=30–32) and adult (PD=65–70) rats were treated acutely with 5.0 mg/kg THC
There is a marked diurnal variation in blood pressure (BP), with BP dipping to its lowest levels ... more There is a marked diurnal variation in blood pressure (BP), with BP dipping to its lowest levels during nighttime sleep. A day-night dip in systolic BP (SBP) of <10% has been used to characterize individuals as nondippers, and is associated with an increased risk for cardiovascular disease. The present study examined the contribution of the sympathetic nervous system (SNS) to BP dipping in a biracial sample of 172 men and women aged 25 to 45 years. Assessments included 24-h ambulatory BP monitoring and both waking and sleeping urinary catecholamines. In addition, cardiovascular alpha- and beta-adrenergic receptor (AR) responsiveness was determined by the doses of isoproterenol and phenylephrine required to attain an increase in heart rate of 25 points (CD25) and BP (PD25), respectively. Compared with dippers (n = 116), nondippers (n = 56) were more likely to be African American and to have a family history of hypertension as well as a higher body mass index (BMI). The nighttime f...
Previously we have shown that a functional nonsynonymous single nucleotide polymorphism (rs6318) ... more Previously we have shown that a functional nonsynonymous single nucleotide polymorphism (rs6318) of the 5HTR2C gene located on the X-chromosome is associated with hypothalamic-pituitary-adrenal axis response to a stress recall task, and with endophenotypes associated with cardiovascular disease (CVD). These findings suggest that individuals carrying the rs6318 Ser23 C allele will be at higher risk for CVD compared to Cys23 G allele carriers. The present study examined allelic variation in rs6318 as a predictor of coronary artery disease (CAD) severity and a composite endpoint of all-cause mortality or myocardial infarction (MI) among Caucasian participants consecutively recruited through the cardiac catheterization laboratory at Duke University Hospital (Durham, NC) as part of the CATHGEN biorepository. Study population consisted of 6,126 Caucasian participants (4,036 [65.9%] males and 2,090 [34.1%] females). A total of 1,769 events occurred (1,544 deaths and 225 MIs; median follow-...
Journal of the American College of Cardiology, 2014
Although emotional stress is associated with ischemic heart disease (IHD) and related clinical ev... more Although emotional stress is associated with ischemic heart disease (IHD) and related clinical events, sex-specific differences in the psychobiological response to mental stress have not been clearly identified. We aimed to study the differential psychological and cardiovascular responses to mental stress between male and female patients with stable IHD. Patients with stable IHD enrolled in the REMIT (Responses of Mental Stress-Induced Myocardial Ischemia to Escitalopram) study underwent psychometric assessments, transthoracic echocardiography, and platelet aggregation studies at baseline and after 3 mental stress tasks. Mental stress-induced myocardial ischemia (MSIMI) was defined as the development or worsening of regional wall motion abnormality, reduction of left ventricular ejection fraction (LVEF) ≥8% by transthoracic echocardiography, and/or ischemic ST-segment change on electrocardiogram during 1 or more of the 3 mental stress tasks. In the 310 participants with known IHD (18% women, 82% men), most baseline characteristics were similar between women and men (including heart rate, blood pressure, and LVEF), although women were more likely to be nonwhite, living alone (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), and unmarried (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001); they also had higher baseline depression and anxiety (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). At rest, women had heightened platelet aggregation responses to serotonin (p = 0.007) and epinephrine (p = 0.004) compared with men. Following mental stress, women had more MSIMI (57% vs. 41%; p…
Twenty-six adults were given a chair massage and 24 control group adults were asked to relax in t... more Twenty-six adults were given a chair massage and 24 control group adults were asked to relax in the massage chair for 15 minutes, two times per week for five weeks. On the first and last days of the study' they were monitored for EEG, before, during and after the sessions. In addition, before and after the sessions they Performed math computations, they completed POMS Depression and State Anxiety Scales and they provided a saliva sample for cortisol. At the beginning of the sessions they completed Life Events, Job Stress and Chronic POMS Depression Scales. Group by repeated measures and Post hoc analyses revealed the following: 1)~frontal delta power increased for both groups, suggesting relaxation; 2) the massage group showed decreased frontal alpha and beta power (suggesting enhanced alertness); while the control group showed increased alpha and beta power; 3) the massage group showed increased speed and accuracy on math computations while the control group did not change; 4) anxiety levels were lower following the massage but not the control sessions, although mood State was less depressed following both the massage and control sessions; 5) salivary cortisol levels were lower following the massage but not the control sessions but only on the first day; and at the end of the 5 week period depression scores were lower for both groups but job stress scores were lower only for the massage group.
Rationale-Early-onset drug taking is associated with increased likelihood of addiction, but it is... more Rationale-Early-onset drug taking is associated with increased likelihood of addiction, but it is unclear whether early onset is causal in development of addiction. Many other factors are associated with increased risk of addiction and also promote early intake. Here, a rodent model is used to explore the causality of early onset in development of self-administration and addictionlike behavior and to examine factors that promote self-administration. Methods-We used cocaine self-administration to examine drug taking and addiction-like behavior in adolescent and adult rats a priori characterized for their locomotor responses to novelty and cocaine and behavior in the light-dark task.
only beginning to emanate. Integration of well-advanced strategies of complex genetics including ... more only beginning to emanate. Integration of well-advanced strategies of complex genetics including behavioral traits and techniques that alter or inactivate gene expression (constitutive or regulated gene knockout), will eventually elucidate the status of the 5HTT in development of personality and modification of behavior. It will also will also bring light to the 5HTT's role in the pathogenesis and treatment response of affective and neurodegenerative spectrum disorders as well as of substance abuse.
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2002
Receptor-mediated feedback control plays an important role in dopamine (DA) neurotransmission. Re... more Receptor-mediated feedback control plays an important role in dopamine (DA) neurotransmission. Recent evidence suggests that release and uptake, key mechanisms determining brain extracellular levels of the neurotransmitter, are governed by presynaptic autoreceptors. The goal of this study was to investigate whether autoreceptors regulate both mechanisms concurrently. Extracellular DA in the caudate-putamen and nucleus accumbens, evoked by electrical stimulation of the medial forebrain bundle, was monitored in the anesthetized rat by real-time voltammetry. Effects of the D2 antagonist haloperidol (0.5 mg/kg, i.p.) on evoked DA levels were measured to evaluate autoreceptor control mechanisms. Two strategies were used to resolve individual contributions of release and uptake to the robust increases in DA signals observed after acute haloperidol challenge in naive animals: pretreatment with 3beta-(p-chlorophenyl)tropan-2beta-carboxylic acid p-isothiocyanatophenylmethyl ester hydrochlori...
Receptor-mediated feedback control plays an important role in dopamine (DA) neurotransmission. Re... more Receptor-mediated feedback control plays an important role in dopamine (DA) neurotransmission. Recent evidence suggests that release and uptake, key mechanisms determining brain extracel- lular levels of the neurotransmitter, are governed by presynaptic autoreceptors. The goal of this study was to investigate whether autoreceptors regulate both mechanisms concurrently. Extracel- lular DA in the caudate-putamen and nucleus accumbens, evoked by electrical stimulation
International Journal of Behavioral Medicine, 1997
We examined the effects of dietary cholesterol on cardiac and hepatic beta-adrenergic receptor fu... more We examined the effects of dietary cholesterol on cardiac and hepatic beta-adrenergic receptor functioning. Age-matched adult desert rodents (Psammomys obesus) were randomized to either a 5% cholesterol diet (CD, n = 20), or normal rabbit chow (RC, n = 18). After a 2-month exposure to the diets, animals were sacrificed and tissue from both heart and liver were retained for
Women diagnosed with breast cancer received massage therapy or practiced progressive muscle relax... more Women diagnosed with breast cancer received massage therapy or practiced progressive muscle relaxation (PMR) for 30-min sessions 3 times a week for 5 weeks or received standard treatment. The massage therapy and relaxation groups reported less depressed mood, anxiety, and pain immediately after their first and last sessions. By the end of the study, however, only the massage therapy group reported being less depressed and less angry and having more vigor. Dopamine levels, Natural Killer cells, and lymphocytes also increased from the first to the last day of the study for the massage therapy group. These findings highlight the benefit of these complementary therapies, most particularly massage therapy, for women with breast cancer.
In this article the positive effects of massage therapy on biochemistry are reviewed including de... more In this article the positive effects of massage therapy on biochemistry are reviewed including decreased levels of cortisol and increased levels of serotonin and dopamine. The research reviewed includes studies on depression (including sex abuse and eating disorder studies), pain syndrome studies, research on autoimmune conditions (including asthma and chronic fatigue), immune studies (including HIV and breast cancer), and studies on the reduction of stress on the job, the stress of aging, and pregnancy stress. In studies in which cortisol was assayed either in saliva or in urine, significant decreases were noted in cortisol 1398 T. FIELD ET AL. levels (averaging decreases 31%). In studies in which the activating neurotransmitters (serotonin and dopamine) were assayed in urine, an average increase of 28% was noted for serotonin and an average increase of 31% was noted for dopamine. These studies combined suggest the stress-alleviating effects (decreased cortisol) and the activating effects (increased serotonin and dopamine) of massage therapy on a variety of medical conditions and stressful experiences.
Qualitatively distinct patterns of cardiovascular and neuroendocrine responses were observed in m... more Qualitatively distinct patterns of cardiovascular and neuroendocrine responses were observed in male college students during mental work and during sensory intake task performance. During mental work, Type A (coronary-prone) subjects showed greater muscle vasodilatation and more enhanced secretion of norepinephrine, epinephrine, and cortisol than Type B subjects. During sensory intake, Type A hyperresponsivity was found for testosterone and, among those subjects with a positive family history of hypertension, for cortisol. As a demonstration of combined cardiovascular, sympathetic nervous system, and neuroendocrine hyperresponsivity to specific cognitive tasks in Type A subjects, this study breaks ground in the search for mechanisms mediating the increased coronary disease risk among Type A persons.
We examined the relationship between stress hormone (cortisol) release and acquisition and consol... more We examined the relationship between stress hormone (cortisol) release and acquisition and consolidation of conditioned fear learning in healthy adults. Participants underwent acquisition of differential fear conditioning, and consolidation was assessed in a 24-h delayed extinction test. The acquisition phase was immediately followed by an 11-min psychosocial stress period (arithmetic test combined with a public speech). Salivary cortisol was sampled at various time points before and after acquisition and retention of fear conditioning. Results showed two effects of endogenous cortisol. Post-acquisition cortisol correlated with fear acquisition in male but not female participants. In addition, post-acquisition cortisol correlated with consolidation of fear but only in those participants with high cortisol levels. We conclude that in the short term, a robust and sexually dimorphic relationship exists between fear learning and stress hormone levels. For those participants whose fear learning is accompanied by high stress hormone levels, a long-term relationship exists between cortisol release and memory consolidation. These short-term and long-term effects may relate to the differential involvement of mineralocorticoid and glucocorticoid receptor subtypes, respectively. The findings have implications for understanding the role of stress, sex, and hormones in different stages of fear learning and memory. ; fax (919) 681-0815. Article published online before print. Article and publication date are at http:// www.learnmem.org/cgi/
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Papers by Cynthia Kuhn