Basolateral amygdala CB1 cannabinoid receptors are involved in cross state-dependent memory retrieval between morphine and ethanol

• Intraperitoneal administration of morphine impaired memory retrieval.
• Intraperitoneal administration of ethanol reversed the amnesic effect of morphine.
• Intra-BLA injection of WIN55,212-2 plus ethanol improved morphine-induced amnesia.
• Blockade of the BLA CB1 receptors reversed the ethanol effects on morphine response.
• Intra-BLA injection of WIN55,212-2 or AM251 had no effects on memory retrieval alone.

Ethanol and morphine are largely co-abused and affect memory formation. The present study intended to investigate the involvement of cannabinoid CB1 receptors of the basolateral amygdala (BLA) in cross state-dependent memory retrieval between morphine and ethanol. Adult male Wistar rats received bilateral cannulation of the BLA, and memory retrieval was measured in step-through type passive avoidance apparatus. Our results showed that post-training intraperitoneal (i.p.) administration of morphine (6 mg/kg) induced amnesia. Pre-test administration of ethanol (0.5 g/kg, i.p.) significantly improved morphine-induced memory impairment, suggesting that there is cross state-dependent memory retrieval between morphine and ethanol. It should be considered that pre-test administration of ethanol (0.1 and 0.5 g/kg, i.p.) by itself had no effect on memory retrieval in the passive avoidance task. Interestingly, pre-test intra-BLA microinjection of different doses of WIN55,212-2 (0.1, 0.2 and 0.3 μg/rat), a non-selective CB1/CB2 receptor agonist, plus an ineffective dose of ethanol (0.1 g/kg, i.p.) improved morphine-induced memory impairment. Intra-BLA microinjection of AM251 (0.4–0.6 ng/rat), a selective CB1 receptor antagonist, inhibited the improved effect of ethanol (0.5 g/kg, i.p.) on morphine response. Pre-test intra-BLA microinjection of WIN55,212-2 or AM251 had no effect on memory retrieval or morphine-induced amnesia. Taken together, it can be concluded that morphine and ethanol can induce state-dependent memory retrieval. In addition, the BLA endocannabinoid system mediates via CB1 receptors the functional interaction of morphine and ethanol state-dependent memory retrieval which may depend on the rewarding effects of the drugs.