Cross state-dependency of learning between morphine and WIN55, 212-2 in mouse dorsal hippocampus

Abstract

Both morphine and cannabinoids impair memory and induce state-dependent learning. Furthermore, early studies indicated the existence of functional interactions between cannabinoid and opioid systems in the modulation of behavioral and physiological responses. Therefore, in the current study, cross state-dependent learning between WIN55, 212-2 (a cannabinoid CB1/CB2 receptor agonist) and morphine (µ-opioid agonist) administration in mice dorsal hippocampus was investigated using a step-down inhibitory avoidance task. Animals were bilaterally implanted with chronic cannulae in the CA1 regions of the dorsal hippocampus, trained in a step-down type inhibitory avoidance task, and tested 24 h after training to measure their step-down latency. Post-training or pre-test administration of morphine (6 mg/kg) and WIN55, 212-2 (0.6 and 0.9 µg/mouse) impaired inhibitory avoidance memory and induced amnesia. Moreover, the amnesia induced by the post-training injections of morphine (6 mg/kg) or WIN55, 212-2(0.9 µg/mouse) was restored by either pre-test injections of morphine (6 mg/kg) or WIN55, 212-2(0.9 µg/mouse). Furthermore, pre-test co-administration of ineffective doses of morphine (3 mg/kg) with WIN55, 212-2 (0.3 µg/mouse) restored the amnesia induced by post-training injections of WIN55, 212-2(0.9 µg/mouse) or morphine (6 mg/kg). Noteworthy, the response induced by the pre-test injection of morphine or WIN55, 212-2 was antagonized with naloxone. Our data strongly revealed a cross state-dependent learning between morphine and WIN55, 212-2 in mice where µ-opioid receptors of dorsal hippocampus play an important role.