Basolateral amygdala involvement in memory reconsolidation processes that facilitate drug context-induced cocaine seeking.

Abstract

Understanding the neurobiological underpinnings of putative memory stabilization processes that maintain context-response-cocaine associations in long-term memory and underlie contextual control over addictive behavior is of great interest from an addiction treatment perspective. Using an instrumental animal model of contextual drug relapse we show that the protein synthesis inhibitor anisomycin, administered into the basolateral amygdala (BLA) immediately after limited (15- or 60-min) re-exposure to a previously cocaine-paired context, subsequently disrupted the ability of the previously cocaine-paired context to reinstate extinguished cocaine-seeking behavior relative to vehicle. Consistent with a BLA-mediated memory reconsolidation deficit, a similar impairment in cocaine-seeking behavior was not observed in (i) 'no-reactivation' control groups that received anisomycin into the BLA after (re)exposure to either a novel unpaired or an extinction-paired context or in (ii) a neuroanatomical control group that received anisomycin into the posterior caudate-putamen, dorsally adjacent to the BLA, after re-exposure to the cocaine-paired context. Furthermore, anisomycin administered into the BLA after brief (5-min) or extensive (120-min) re-exposure to the cocaine-paired context (which was sufficient to extinguish cocaine-seeking behavior in a vehicle control group) also failed to alter responding. Together, these findings suggest that re-exposure to a cocaine-paired context in the absence of cocaine reinforcement is sufficient to trigger memory reconsolidation processes that support future drug-seeking behavior. The presence and duration of drug-related memory reactivation critically influences, and anisomycin-sensitive mechanisms in the BLA selectively control, this phenomenon. These findings support the feasibility of novel pharmacotherapeutic approaches that selectively inhibit the reconsolidation of cocaine-related memories in order to prevent drug relapse.