Involvement of cannabinoid receptors in the amygdala and prefrontal cortex of rats in fear learning, consolidation, retrieval and extinction

•Drug study on fear memory and cannabinoids in prefrontal cortex and amygdala.•Cannabinoids reduce fear learning in amygdala and prefrontal cortex.•Cannabinoid antagonists impair fear extinction in the prefrontal cortex. Cannabinoid receptors 1 (CB1R) have been shown to be a crucial part of the neuromodulatory endocannabinoid system which is involved in emotional learning and memory. We here investigated in rats the role of CB1R in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) in different phases of fear learning, memory and extinction. We used the fear potentiated startle paradigm to measure the effects of local microinfusion of the CB1R agonist WIN 55,212-2 (WIN) or the CB1R antagonist AM251 on acquisition, consolidation, retrieval and extinction of fear. No effects on fear acquisition of WIN or AM251 were found in the BLA or mPFC. WIN impaired fear retrieval in the BLA and in mPFC. Also, WIN reduced fear consolidation in the BLA but not in the mPFC. AM251 decreased fear consolidation after mPFC infusion. Likewise, fear extinction was impaired by AM251 infused into the mPFC. Our data indicate that fear memory consolidation and retrieval, as well as extinction are regulated differentially by amygdaloid and cortical CB1R.