The role of the basolateral amygdala in stimulus–reward memory and extinction memory consolidation and in subsequent conditioned cued reinstatement of cocaine seeking

Abstract

The consolidation of cue-cocaine associations and extinction learning (i.e. cue-no cocaine associations) into long-term memory probably regulates the long-lasting control of conditioned stimuli (CS) over cocaine-seeking behaviour, and the basolateral amygdala (BLA) may play a role in this phenomenon. To test this hypothesis, rats previously trained to self-administer cocaine underwent a single classical conditioning (CC) session, during which they received passive pairings of cocaine infusions and a novel light + tone stimulus complex. After additional self-administration sessions in the absence of CS presentation and subsequent extinction training sessions, the ability of the CS to reinstate cocaine-seeking on five test days was assessed. Rats received intra-BLA microinfusions of vehicle or the Na+-channel blocker tetrodotoxin (TTX) immediately after CC (consolidation of CS-cocaine associations) or immediately after reinstatement testing (consolidation of extinction learning). TTX administered immediately after CC attenuated subsequent CS-induced reinstatement. In contrast, TTX administered after the first reinstatement test impaired the extinction of cocaine-seeking behaviour during a second reinstatement test by disrupting extinction memory. Overall, these findings suggest that Na+ channel-mediated mechanisms within the BLA mediate the consolidation of both cocaine-stimulus association and extinction learning, two processes that have opposite effects on subsequent cue-induced cocaine-seeking behaviour.