Interaction of Basolateral Amygdala and Prelimbic Cortex Glucocorticoid Receptors with the Endocannabinoid System in Inhibitory Avoidance Memory Consolidation in Rats

Considering the crucial neuromodulatory role of cannabinoid and glucocorticoid signaling in the memory processing, the putative interaction of these two systems in the prelimbic area (PL) and basolateral amygdala (BLA) remains unclear. We here used the inhibitory avoidance paradigm to investigate whether glucocorticoid receptor (GR) antagonist, RU38486 (RU) and the cannabinoid receptor type 1 (CB1r) agonist, WIN55, 212-2 (WIN) administration in the PL and BLA can modulate inhibitory avoidance memory (IA) memory consolidation in male rats. Adult male rats (n = 42) were randomly divided into six equal groups. Four groups were given intra BLA and/or intra-PL injections of RU (3 ng/side) and WIN (5 µg/side). The other two groups received systemic injections of WIN55, 212-2 (0.5 mg/kg) immediately after training in a IA task and the percentage of freezing time in the IA test was recorded 24 h after training. Whilst intra-BLA RU and WIN infusion after IA training impaired memory consolidation, intra PL administration of WIN at the same dose increased the traumatic memory consolidation. Furthermore, RU combined with WIN in PL attenuated this response suggesting the effects of WIN mediated via GR in PL but not in BLA. In addition, post-training systemic administration of WIN inhibited the up-regulation of CB1 receptor levels in the PL, in the BLA, and GR receptors in BLA but not PL induced in shock experienced rats. Our observations introduce cannabinoids and glucocorticoids in the PL and BLA as main contributors in consolidation of aversive memories introducing a novel strategy for emotional diseases therapy and particularly traumatic events.