Reversible inactivation of the basolateral amygdala, but not the dorsolateral caudate putamen, attenuates consolidation of cocaine-cue associative learning in a reinstatement model of drug-seeking

Eur J Neurosci. 2010 Sep;32(6):1024-9. doi: 10.1111/j.1460-9568.2010.07394.x. Epub 2010 Aug 26.

Abstract

Previous research has shown that the basolateral amygdala (BLA) mediates stimulus-reward learning, including drug-cue associations, whereas the dorsolateral caudate putamen (dlCPu) primarily mediates stimulus-response (habit) learning. Recent evidence has indicated that the dlCPu may be critical in cocaine-seeking following extended self-administration, but it remains unknown whether the dlCPu plays a role in the early formation of drug-cue associations. The current study used a model of Pavlovian learning to compare the roles of the BLA and dlCPu in the consolidation of cocaine-cue associations that maintain cocaine-seeking during cue-induced reinstatement. Male Sprague-Dawley rats self-administered cocaine (0.2 mg/ 50μL infusion, i.v.) in the absence of cues for 6 days (2 h/day). Immediately following a single 1-h classical conditioning session in which passive cocaine infusions were paired with a light/tone cue, animals received bilateral infusions of the GABA receptor agonists, baclofen/muscimol (1.0/0.1 mm), or vehicle into the BLA or dlCPu. Following additional cocaine self-administration (5 days) and subsequent extinction (no cocaine or cues, 7 days), the ability of the previously cocaine-paired cues to reinstate cocaine-seeking was assessed. Inactivation of the BLA, but not the dlCPu, immediately following the classical conditioning session impaired the consolidation of cocaine-cue associations as seen by decreased cue-induced reinstatement. These results extend previous findings that the BLA mediates the consolidation of learned associations that drive cocaine-seeking during subsequent reinstatement and indicate that the dlCPu does not play a role during initial stimulus-drug associative learning.

Publication types

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

MeSH terms

  • Amygdala / drug effects
  • Amygdala / physiology*
  • Animals
  • Association Learning / drug effects
  • Association Learning / physiology*
  • Behavior, Addictive / physiopathology
  • Behavior, Addictive / psychology*
  • Caudate Nucleus / drug effects
  • Caudate Nucleus / physiology*
  • Cocaine / administration & dosage*
  • Conditioning, Classical / drug effects
  • Conditioning, Classical / physiology
  • Cues
  • Male
  • Models, Animal
  • Putamen / drug effects
  • Putamen / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Self Administration

Substances

  • Cocaine