GABAA receptors in the central amygdala are involved in memory retention deficits induced by cannabinoids in rats

•WIN55, 212-2 injection to CeA impaired memory retrieval in passive avoidance task.•Pre-test injection of muscimol and bicuculline did not alter STLr in retention test.•Muscimol (125 ng/rat) potentiated the amnestic effects of WIN55, 212-2.•Bicuculline (200 ng/rat) attenuated WIN 55, 212-2-induced memory deficits.•Bicuculline prevented muscimol-induced potentiating on WIN 55, 212-2 effects.

The central nucleus of the amygdala (CeA) as the main output of amygdala plays an important role in memory processes. In this study we first evaluated the effects of intra-CeA administrations of different doses of a cannabinoid CB1 agonist, WIN55, 212-2, GABAA receptor agonist and antagonist, muscimol and bicuculline, alone on memory retention using passive avoidance learning (PAL) test in rats. Then we examined the effects of GABAA receptor agents on the responses induced by intra-CeA microinjection of different doses of WIN55, 212-2. We found that administration of WIN55, 212-2 (0.05, 0.1, 0.2 and 0.4 μg/rat) immediately after training impaired memory retrieval in a dose-dependent fashion. Although pre-test intra-CeA administration of muscimol (125, 250 and 500 ng/rat) alone had no effect on the step-through latency, its co-administration (125 ng/rat) with different doses of WIN55, 212-2 potentiated the amnesic effects of any doses of WIN55, 212-2. The results also showed that pre-test intra-CeA administration of bicuculline (200, 400 and 800 ng/rat) alone had no significant effect, but at dose of 200 ng/rat disrupted post-training WIN55, 212-2-induced amnesia in the retention test. Furthermore, the additional effect of muscimol (125 ng/rat) on memory impairment induced by WIN55, 212-2 (0.1 μg/rat) was prevented by intra-CeA co-injection of bicuculline (200 ng/rat). We indicated that stimulating or blocking GAGAA receptors in the CeA by muscimol and bicuculline interfere with WIN55, 212-2-induced deficits in memory retention in a PAL task and therefore suggests an interaction between cannabinergic and GABAergic systems of the CeA in memory process.