Basolateral amygdala corticotropin-releasing factor receptor type 1 regulates context-cocaine memory strength during reconsolidation in a sex-dependent manner

The basolateral amygdala (BLA) is a critical brain region for cocaine-memory reconsolidation. Corticotropinreleasing factor receptor type 1 (CRFR1) is densely expressed in the BLA, and CRFR1 stimulation can activate intra-cellular signaling cascades that mediate memory reconsolidation. Hence, we tested the hypothesis that BLA CRFR1 stimulation is necessary and sufficient for cocaine-memory reconsolidation. Using an instrumental model of drug relapse, male and female Sprague-Dawley rats received cocaine self-administration training in a distinct environmental context over 10 days followed by extinction training in a different context over 7 days. Next, rats were re-exposed to the cocaine-paired context for 15 min to initiate cocaine-memory retrieval and destabilization. Immediately or 6 h after this session, the rats received bilateral vehicle, antalarmin (CRFR1 antagonist; 500 ng/hemisphere), or corticotropin-releasing factor (CRF; 0.2, 30 or 500 ng/hemisphere) infusions into the BLA. Resulting changes in drug context-induced cocaine seeking (index of context-cocaine memory strength) were assessed three days later. Female rats self-administered more cocaine infusions and exhibited more extinction responding than males. Intra-BLA antalarmin treatment immediately after memory retrieval (i.e., when cocaine memories were labile), but not 6 h later (i.e., after memory reconsolidation), attenuated drug context-induced cocaine seeking at test independent of sex, relative to vehicle. Conversely, intra-BLA CRF treatment increased this behavior selectively in females, in a U-shaped dose-dependent fashion. In control experiments, a high (behaviorally ineffective) dose of CRF treatment did not reduce BLA CRFR1 cell-surface expression in females. Thus, BLA CRFR1 signaling is necessary and sufficient, in a sex-dependent manner, for regulating cocainememory strength.

Automated summary

The study found that CRFR1 signaling in the brain region BLA is crucial for regulating the strength of cocaine memories in rats, with potential sex differences in its effects.