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

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.

Figure 1

Schematic diagram of coronal sections (anterior–posterior from bregma) of infusion cannulae placements for the basolateral amygdala (left) and the dorsolateral caudate putamen (right) (adapted from Paxinos & Watson, 1997).

Figure 2

Mean (±SEM) active (top) and inactive (bottom) lever responses for the last two days of self-administration (SA) phases I and II, extinction (EXT), and during the CS-reinstatement test. Animals received bilateral intra-BLA infusions of vehicle or B/M immediately following the CC session. Significant differences are indicated as compared to extinction levels (*P < 0.05) or vehicle (†P < 0.05).

Figure 3

Mean (±SEM) active (top) and inactive (bottom) lever responses for the last two days of self-administration (SA) phases I and II, extinction (EXT), and during the CS-reinstatement test. Animals received bilateral intra-CPu infusions of vehicle or B/M immediately following the CC session. Significant differences are indicated as compared to extinction levels (*P < 0.01).