Environmental enrichment counters cocaine abstinence-induced stress and brain reactivity to cocaine cues but fails to prevent the incubation effect

Addict Biol. 2012 Mar;17(2):365-77. doi: 10.1111/j.1369-1600.2011.00358.x. Epub 2011 Aug 4.

Abstract

Environmental enrichment (EE) during a period of forced abstinence attenuates incentive motivational effects of cocaine-paired stimuli. Here we examined whether EE during forced abstinence from cocaine self-administration would prevent time-dependent increases in cue-elicited cocaine-seeking behavior (i.e. the incubation effect). Rats were trained to self-administer cocaine, which was paired with light/tone cues, for 15 days while living in isolated conditions (IC). Controls received yoked saline infusions. Subsequently, rats were assigned to live in either continued IC or EE for either 1 or 21 days of forced abstinence prior to a test for cocaine-seeking behavior. During testing, responding resulted only in presentation of the light/tone cues. Contrary to our prediction, cocaine-seeking behavior increased over time regardless of living condition during abstinence; however, EE attenuated cocaine-seeking behavior relative to IC regardless of length of abstinence. Brains were harvested and trunk blood was collected immediately after the 60-minute test and later assayed. Results indicated that short-term EE elevated hippocampal brain-derived neurotrophic factor and reduced plasma corticosterone compared with IC. Furthermore, 21 days of EE during forced abstinence prevented increases in the cue-elicited amygdala phosphorylated extracellular signal-regulated kinase expression that was observed in IC rats. These findings suggest that EE attenuates incentive motivational effects of cocaine cues through a mechanism other than preventing the incubation effect, perhaps involving reduction of stress and neural activity in response to cocaine-paired cues during acute withdrawal.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cocaine / administration & dosage
  • Cocaine / pharmacology
  • Cocaine-Related Disorders / psychology*
  • Conditioning, Operant / drug effects
  • Corticosterone / metabolism
  • Cues*
  • Drug-Seeking Behavior / drug effects*
  • Environment*
  • Extinction, Psychological / drug effects
  • In Vitro Techniques
  • MAP Kinase Signaling System / physiology
  • Male
  • Motivation / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Self Administration
  • Social Isolation / psychology*
  • Stress, Psychological / prevention & control*
  • Substance Withdrawal Syndrome / psychology
  • eIF-2 Kinase / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • PERK kinase
  • eIF-2 Kinase
  • Cocaine
  • Corticosterone
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