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, similar impairment in cocaine-seeking behavior was not observed in "no-reactivation" control groups that received anisomycin into the BLA after (re)exposure to either a novel unpaired or an extinctionpaired context nor in 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) reexposure 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.

Updating memories—The role of prediction errors in memory reconsolidation

“…A second concern with this finding, is whether the results are mediated by a change in instrumental memory strength. Importantly, the changes observed in performance could have been mediated by modulation of an incentive, contextual or motivational process instead of an instrumental association; the memories underpinning incentive learning [109,132], conditioned reinforcement [67,83,112] and the conditioned motivational properties of stimuli [63,84] and contexts [43] are all known to undergo reconsolidation. All these processes, in addition to the underlying instrumental memory, contribute to the final behavioural output.…”

Extracellular Signal-Regulated Kinase in the Basolateral Amygdala, but not the Nucleus Accumbens Core, is Critical for Context-Response-Cocaine Memory Reconsolidation in Rats

“…Forty-eight hours later, they were surgically implanted with intravenous jugular catheters and twenty-six gauge stainless steel guide cannulae (Plastics One) aimed bilaterally either at the BLA ( À 2.7 mm AP, ± 5.1 mm ML, À 6.7 mm DV, relative to bregma) or the NACc (angled laterally by 101; þ 1.4 mm AP, ± 3.1 ML, À 4.8 mm DV, relative to bregma). The food training, surgery, and post-operative care procedures have been described previously (Fuchs et al, 2009). …”

“…However, the role of ERK in the reconsolidation of contextual drug memories has not been assessed in an instrumental paradigm. Hence, the present study utilized the extinction-reinstatement model of environmentally triggered drug relapse in order to determine whether ERK signaling would be required for the reconsolidation of context-response-cocaine memories in two brain regions that critically regulate drug-memory reconsolidation: the basolateral amygdala (BLA; Sanchez et al, 2010;Li et al, 2010;Fuchs et al, 2009) and the nucleus accumbens core (NACc; Miller and Marshall, 2005;Théberge et al, 2010).…”

Post-Retrieval Extinction Attenuates Cocaine Memories

“…This labile property, termed reconsolidation, is a time-dependent process (o6 h), in which consolidated memories become transiently unstable shortly after retrieval and are susceptible to updating or disruption. In recent years, several studies have exploited this reconsolidation process by injecting animals with amnestic agents either before or immediately after retrieval (during reconsolidation) to attenuate previously consolidated drug-related memories (Lee et al, 2005;Lee et al, 2006;Valjent et al, 2006;Fricks-Gleason and Marshall, 2008;Milton et al, 2008;Fuchs et al, 2009;Sanchez et al, 2010). However, many of these amnestic agents (eg, protein synthesis inhibitors) are not suitable for human use, and thus other reconsolidation-based behavioral or pharmaceutical avenues are needed for the treatment of addiction.…”