Influence of WIN55, 212-2 on morphine state-dependent memory in the step-down passive avoidance test

Both endogenous cannabinoids and opiate substances have high levels of expression in the brain and may have important neuromodulatory functions. The present study evaluated the possible role of cannabinoid system of the dorsal hippocampus in morphine induced amnesia and morphine state-dependent memory in adult male mice. In this experimental study 255 adult male NMRI mice were anaesthetized and put into a stereotaxic device and cannula were implanted bilaterally in the CA1 regions of their dorsal hippocampus. Seven days after recovery from surgery, the behavioral testing was started by use of inhibitory avoidance task. In this study morphine and WIN55, 212-2 was used as opioid receptor agonist and cannabinoid receptor agonist respectively. Intra peritoneal (i.p.) administration of morphine immediately after training, decreased memory formation in a dose-dependent way (P<0.01). Amnesia induced by post-training morphine injection was reversed by pre-test administration of the same dose of morphine that is due to a state-dependent effect (P<0.001). Pre-test intra-CA1 administration of WIN55 212-2 after training, reversed amnesia induced by morphine and restored normal memory state (P<0.001). The results of this study suggested that cannabinoid receptors of the dorsal hippocampal CA1 regions might play an important role in morphine-induced amnesia and morphine state-dependent memory.