Effect of cannabinoidergic drugs in the dorsal hippocampus of morphine sensitized rats in the memory formation.

In present study, the effects of intra-dorsal hippocampal (intra-CA1) injection of cannabinoid receptor agents on memory formation have been investigated in 3-days morphine-treated rats. Passive avoidance task of memory has been used to examine for retrieval of memory formation, 24 h after training. morphine was injected subcutaneously (S.C.), once daily for 3-days followed by 5 days free of the morphine before training. Post-training intra–CA1 administration of cannabinoid receptor agonist, WIN55, 212-2 (0.25 and 0.5 µg/rat) and CB1 receptor antagonist, AM251 (25 and 50 ng/rat, intra–CA1) decreased memory retrieval. Administration of AM251 (25, 50 and 100 ng/rat, intra – CA1), 2 min before injection of effective dose of WIN55, 212-2 (0.5 µg/rat) decreased the response induced by WIN55, 212-2. Repeated administration of different doses of morphine (2.5, 5 and 10 mg /kg) for 3-days incraesed memory retrieval. However, repeated administration of different doses of morphine (2.5, 5 and 10 mg /kg) for 3-days reversed amnesia induced by WIN55, 212-2. The results suggest that cannabinoidergic and opioidegic system have a close interaction on memory retrieval and WIN55,212-2 influence on memory formation and subchronic morphine pre-treatment may restore memory through a possible opioidergic receptor sensitization.