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Differential neurochemical and behavioral adaptation to cocaine after response contingent and noncontingent exposure in the rat

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Abstract

Rationale

In naive rats, passive administration of drugs of abuse preferentially increases extracellular dopamine (DA) in the nucleus accumbens (NAc) shell as compared to the core. Repeated exposure to the same drugs results in behavioral and biochemical sensitization characterized by stereotyped activity and reduction of the shell/core DA response ratio.

Objectives

The aim of this work is to study the neurochemical and behavioral effects of response-contingent vs response-noncontingent drug administration in rats, who were bilaterally implanted with chronic intracerebral guide cannulae and trained to self-administer cocaine by nose poking in daily 1-h sessions for 3 weeks (5 days/week). Nose poking in the active hole by master rats resulted in intravenous injection of cocaine (0.25 mg/kg) in master rats and in rats yoked to them. Dialysate DA was monitored before, during, and for 30 min after cocaine availability on alternate days by inserting the probe into the NAc shell and core. Stereotyped and non-stereotyped behavior was recorded during the sessions.

Results

In master rats, dialysate DA increased preferentially in the NAc shell during cocaine self-administration throughout the 3 weeks of cocaine exposure. In yoked rats, DA increased preferentially in the shell but to a lesser extent than in master rats. With continued exposure to cocaine, the shell/core ratio of DA changes decreased progressively and, on the third week, was reversed so that DA increased more in the core than in the shell. Yoked rats showed a progressive and faster increase in stereotyped behaviors than master rats.

Conclusions

Response-noncontingent cocaine administration is particularly prone, compared to response-contingent administration, to induce behavioral and biochemical sensitization.

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References

  • Bassareo V, Di Chiara G (1997) Differential influence of associative and nonassociative learning mechanisms on the responsiveness of prefrontal and accumbal dopamine transmission to food stimuli in rats fed ad libitum. J Neurosci 17:851–861

    PubMed  CAS  Google Scholar 

  • Bassareo V, Di Chiara G (1999) Differential responsiveness of dopamine transmission to food-stimuli in nucleus accumbens shell/core compartments. Neuroscience 89:637–641

    Article  PubMed  CAS  Google Scholar 

  • Bassareo V, De Luca MA, Di Chiara G (2002) Differential expression of motivational stimulus properties by dopamine in nucleus accumbens shell versus core and prefrontal cortex. J Neurosci 22:4709–4719

    PubMed  CAS  Google Scholar 

  • Bordi F, Carr KD, Meller E (1989) Stereotypies elicited by injection of N-propylnorapomorphine into striatal subregions and nucleus accumbens. Brain Res 489:205–215

    Article  PubMed  CAS  Google Scholar 

  • Bradberry CW, Barrett-Larimore RL, Jatlow P, Rubino SR (2000) Impact of self-administered cocaine and cocaine cues on extracellular dopamine in mesolimbic and sensorimotor striatum in rhesus monkeys. J Neurosci 20:3874–3883

    PubMed  CAS  Google Scholar 

  • Cadoni C, Solinas M, Di Chiara G (2000) Psychostimulant sensitization: differential changes in accumbal shell and core dopamine. Eur J Pharmacol 388:69–76

    Article  PubMed  CAS  Google Scholar 

  • Cadoni C, Solinas M, Valentini V, Di Chiara G (2003) Selective psychostimulant sensitization by food restriction: differential changes in accumbens shell and core dopamine. Eur J Neurosci 18:2326–2334

    Article  PubMed  Google Scholar 

  • Cameron DL, Crocker AD (1988) Alkylation of striatal dopamine receptors abolishes stereotyped behavior but has no effect on dopamine stimulated adenylate cyclase activity. Neurosci Lett 90:165–171

    Article  PubMed  CAS  Google Scholar 

  • Camp DM, Robinson TE (1992) On the use of multiple probe insertions at the same site for repeated intracerebral microdialysis experiments in the nigrostriatal dopamine system of rats. J Neurochem 58:1706–1715

    Article  PubMed  CAS  Google Scholar 

  • Carboni E, Acquas E, Frau R, Di Chiara G (1989) Differential inhibitory effects of a 5-HT3 antagonist on drug-induced stimulation of dopamine release. Eur J Pharmacol 164:515–519

    Article  PubMed  CAS  Google Scholar 

  • Carboni E, Spielewoy C, Vacca C, Nosten-Bertrand M, Giros B, Di Chiara G (2001) Cocaine and amphetamine increase extracellular dopamine in the nucleus accumbens of mice lacking the dopamine transporter gene. J Neurosci 21:RC141–RC144

    PubMed  Google Scholar 

  • Cass WA, Gerhardt GA, Mayfield RD, Curella P, Zahniser NR (1992) Differences in dopamine clearance and diffusion in rat striatum and nucleus accumbens following systemic cocaine administration. J Neurochem 59:259–266

    Article  PubMed  CAS  Google Scholar 

  • Deroche V, Marinelli M, Maccari S, Le Moal M, Simon H, Piazza PV (1995) Stress-induced sensitization and glucocorticoids. I. Sensitization of dopamine-dependent locomotor effects of amphetamine and morphine depends on stress-induced corticosterone secretion. J Neurosci 15:7181–7188

    PubMed  CAS  Google Scholar 

  • Di Chiara G (1998) A motivational learning hypothesis of the role of mesolimbic dopamine in compulsive drug use. J Psychopharmacol 12:54–67

    PubMed  Google Scholar 

  • Di Chiara G (2002a) Nucleus accumbens shell and core dopamine: differential role in behavior and addiction. Behav Brain Res 137:75–114

    Article  PubMed  Google Scholar 

  • Di Chiara G (2002b) From rats to humans and return: testing addiction hypotheses by combined PET imaging and self-reported measures of psychostimulant effects. Commentary on Volkow et al. ‘Role of dopamine in drug reinforcement and addiction in humans: results from imaging studies’. Behav Pharmacol 13:371–377

    PubMed  Google Scholar 

  • Di Chiara G, Imperato A (1988) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci USA 85:5274–5278

    Article  PubMed  Google Scholar 

  • Di Chiara G, Tanda G, Carboni E (1996) Estimation of in-vivo neurotransmitter release by brain microdialysis: the issue of validity. Behav Pharmacol 7:640–657

    Article  PubMed  Google Scholar 

  • Di Chiara G, Bassareo V, Fenu S, De Luca MA, Spina L, Cadoni C, Acquas E, Carboni E, Valentini V, Lecca D (2004) Dopamine and drug addiction: the nucleus accumbens shell connection. Neuropharmacology 47:227–241

    Article  PubMed  CAS  Google Scholar 

  • Dickinson A, Balleine B (1994) Motivational control of goal-directed action. Anim Learn Behav 22:1–18

    Google Scholar 

  • Drevets WC, Gautier C, Price JC, Kupfer DJ, Kinahan PE, Grace AA, Price JL, Mathis CA (2001) Amphetamine-induced dopamine release in human ventral striatum correlates with euphoria. Biol Psychiatry 49:81–96

    Article  PubMed  CAS  Google Scholar 

  • Dworkin SI, Mirkis S, Smith JE (1995) Response-dependent versus response-independent presentation of cocaine: differences in the lethal effects of the drug. Psychopharmacology (Berl) 117:262–266

    Article  CAS  Google Scholar 

  • Fumero B, Guadalupe T, Valladares F, Mora F, O’Neill RD, Mas M, Gonzalez-Mora JL (1994) Fixed versus removable microdialysis probes for in vivo neurochemical analysis: implications for behavioral studies. J Neurochem 63:1407–1415

    Article  PubMed  CAS  Google Scholar 

  • Georgieva J, Luthman J, Mohringe B, Magnusson O (1993) Tissue and microdialysate changes after repeated and permanent probe implantation in the striatum of freely moving rats. Brain Res Bull 31:463–470

    Article  PubMed  CAS  Google Scholar 

  • Hemby SE, Martin TJ, Co C, Dworkin SI, Smith JE (1995) The effects of intravenous heroin administration on extracellular nucleus accumbens dopamine concentrations as determined by in vivo microdialysis. J Pharmacol Exp Ther 273:591–598

    PubMed  CAS  Google Scholar 

  • Hemby SE, Co C, Koves TR, Smith JE, Dworkin SI (1997) Differences in extracellular dopamine concentrations in the nucleus accumbens during response-dependent and response-independent cocaine administration in the rat. Psychopharmacology (Berl) 133:7–16

    Article  CAS  Google Scholar 

  • Hooks MS, Duffy P, Striplin C, Kalivas PW (1994) Behavioral and neurochemical sensitization following cocaine self-administration. Psychopharmacology (Berl) 115:265–272

    Article  CAS  Google Scholar 

  • Ito R, Dalley JW, Howes SR, Robbins TW, Everitt BJ (2000) Dissociation in conditioned dopamine release in the nucleus accumbens core and shell in response to cocaine cues and during cocaine-seeking behavior in rats. J Neurosci 20:7489–7495

    PubMed  CAS  Google Scholar 

  • Jacobs EH, Smit AB, de Vries TJ, Schoffelmeer AN (2005) Long-term gene expression in the nucleus accumbens following heroin administration is subregion-specific and depends on the nature of drug administration. Addict Biol 10(1):91–100, Mar

    Article  PubMed  CAS  Google Scholar 

  • Kelly PH (1975) Unilateral 6-hydroxydopamine lesions of nigrostriatal or mesolimbic dopamine-containing terminals and the drug-induced rotation of rats. Brain Res 100:163–169

    Article  PubMed  CAS  Google Scholar 

  • Lecca D, Cacciapaglia F, Valentini V, Gronli J, Spiga S, Di Chiara G (2006a) Preferential increase of extracellular dopamine in the rat nucleus accumbens shell as compared to that in the core during acquisition and maintenance of intravenous nicotine self-administration. Psychopharmacology (Berl) 184:435–446

    Article  CAS  Google Scholar 

  • Lecca D, Cacciapaglia F, Valentini V, Di Chiara G (2006b) Monitoring extracellular dopamine in the rat nucleus accumbens shell and core during acquisition and maintenance of intravenous WIN 55,212-2 self-administration. Psychopharmacology (Berl) DOI 10.1007/s00213-006-0475-3

  • Longoni R, Spina L, Mulas A, Carboni E, Garau L, Melchiorri P, Di Chiara G (1991) (D-Ala2)deltorphin II: D1-dependent stereotypies and stimulation of dopamine release in the nucleus accumbens. J Neurosci 11:1565–1576

    PubMed  CAS  Google Scholar 

  • Marshall JF, O’Dell SJ, Navarrete R, Rosenstein AJ (1990) Dopamine high-affinity transport site topography in rat brain: major differences between dorsal and ventral striatum. Neuroscience 37:11–21

    Article  PubMed  CAS  Google Scholar 

  • Martin-Fardon R, Sandillon F, Thibault J, Privat A, Vignon J (1997) Long-term monitoring of extracellular dopamine concentration in the rat striatum by a repeated microdialysis procedure. J Neurosci Methods 72:123–135

    Article  PubMed  CAS  Google Scholar 

  • Moore H, Stuckman S, Sarter M, Bruno JP (1995) Stimulation of cortical acetylcholine efflux by FG 7142 measured with repeated microdialysis sampling. Synapse 21:324–331

    Article  PubMed  CAS  Google Scholar 

  • O’Brien (2001) In: Hardman JG, Gilman AG, Limbird LE (eds) Goodman & Gilman’s-the pharmacological basis of therapeutics. McGraw-Hill, New York

    Google Scholar 

  • Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates. Academic, Sydney

    Google Scholar 

  • Pettit HO, Justice JB Jr (1989) Dopamine in the nucleus accumbens during cocaine self-administration as studied by in vivo microdialysis. Pharmacol Biochem Behav 34:899–904

    Article  PubMed  CAS  Google Scholar 

  • Pettit HO, Justice JB Jr (1991) Effect of dose on cocaine self-administration behavior and dopamine levels in the nucleus accumbens. Brain Res 539:94–102

    Article  PubMed  CAS  Google Scholar 

  • Pontieri FE, Tanda G, Orzi F, Di Chiara G (1996) Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs. Nature 382:255–257

    Article  PubMed  CAS  Google Scholar 

  • Reid MS, Ciplet D, O’Leary S, Branchey M, Buydens-Branchey L, Angrist B (2004) Sensitization to the psychosis-inducing effects of cocaine compared with measures of cocaine craving and cue reactivity. Am J Addict 13:305–315

    Article  PubMed  Google Scholar 

  • Robinson TE, Camp DM (1991) The feasibility of repeated microdialysis for within-subjects design experiments: studies on mesostriatal dopamine system. In: Robinson TE and Justice JB (eds) Microdialysis in the Neurosciences. Elsevier Science Publishers BV, Amsterdam pp 189–234

    Google Scholar 

  • Rothman RB, Gorelick DA, Baumann MH, Guo XY, Herning RI, Pickworth WB, Gendron TM, Koeppl B, Thomson LE 3rd, Henningfield JE (1994) Lack of evidence for context-dependent cocaine-induced sensitization in humans: preliminary studies. Pharmacol Biochem Behav 49:583–588

    Article  PubMed  CAS  Google Scholar 

  • Satel SL, Southwick SM, Gawin FH (1991) Clinical features of cocaine-induced paranoia. Am J Psych 148:495–498

    CAS  Google Scholar 

  • Volkow ND, Fowler JS, Wang GJ (2002) Role of dopamine in drug reinforcement and addiction in humans: results from imaging studies. Behav Pharmacol 13:355–366

    PubMed  CAS  Google Scholar 

  • Wise RA, Newton P, Leeb K, Burnette B, Pocock D, Justice JB Jr (1995) Fluctuations in nucleus accumbens dopamine concentration during intravenous cocaine self-administration in rats. Psychopharmacology (Berl) 120:10–20

    Article  CAS  Google Scholar 

  • Wu Q, Reith ME, Kuhar MJ, Carroll FI, Garris PA (2001) Preferential increases in nucleus accumbens dopamine after systemic cocaine administration are caused by unique characteristics of dopamine neurotransmission. J Neurosci 21:6338–6347

    PubMed  CAS  Google Scholar 

  • Zapata A, Chefer VI, Ator R, Shippenberg TS, Rocha BA (2003) Behavioural sensitization and enhanced dopamine response in the nucleus accumbens after intravenous cocaine self-administration in mice. Eur J Neurosci 17:590–596

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors gratefully acknowledge the supply of the self-administration cages by Dr. Steve Goldberg and Dr. Gianluigi Tanda. We also thank Mrs. Elena Sias for the excellent technical assistance. This study was supported by funds from Ministero dell’Università e della Ricerca, progetti di Ricerca Nazionale Bando 2003, from the Centre of Excellence for Studies On Dependence and from the European Commission, NIDE project.

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Authors and Affiliations

  1. Department of Toxicology, University of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy

    Daniele Lecca, Fabio Cacciapaglia, Valentina Valentini, Elio Acquas & Gaetano Di Chiara

  2. Centre of Excellence for Studies on the Neurobiology of Addiction, University of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy

    Daniele Lecca, Valentina Valentini, Elio Acquas & Gaetano Di Chiara

  3. Institute of Neuroscience, Consiglio Nazionale delle Ricerche (CNR), Section of Cagliari, Cagliari, Italy

    Gaetano Di Chiara

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  1. Daniele Lecca
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Correspondence to Gaetano Di Chiara.

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Lecca, D., Cacciapaglia, F., Valentini, V. et al. Differential neurochemical and behavioral adaptation to cocaine after response contingent and noncontingent exposure in the rat. Psychopharmacology 191, 653–667 (2007). https://doi.org/10.1007/s00213-006-0496-y

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