The Impact of the Injection of Cannabinoidergic Drugs in the Dorsal hippocampus on the Memory Retrieval of Dopamine Sensitized Rats

In present study, the effects of intra-dorsal hippocampal (intra-CA1) injection of cannabinoid receptor agents on memory retrieval have been investigated in 3-days apomorphine-treated rats. Passive avoidance task of memory has been used to examine the memory retrieval, 24 h after training. Apomorphine was injected subcutaneously (S.C.), once daily for 3-days followed by 5 days free of the apomorphine before training. Post-training intra-CA1 infusions of the non-selective CB1-CB2 receptor agonist, WIN55, 212-2 (0.1, 0.25 and 0.5 µg/rat), dose-dependently shortened the step-through latency, suggesting impaired memory retrieval, whereas post-training intra-CA1 micro-injections of the selective CB1 receptor antagonist, AM251 (25, 50 and 100 ng/rat) did not affect memory retrieval. Intra-CA1 infusions of AM251 and WIN55, 212-2, two min apart, did not modify the WIN55, 212-2-induced reduction of step-through latency. However, the deleterious effect of WIN55, 212-2 (0.25 µg/rat) was completely abolished in rats previously given apomorphine (0.5 and 1 mg/kg/day, S.C.) for 3 days. This reversal of WIN55, 212-2-induced amnestic-like effect was counteracted by the dopamine D2 receptor antagonist, sulpiride (0.25, 0.5 and 1 mg/kg/day×3-days, S.C.), administered 30 min before each injection of apomorphine (0.5 mg/kg/day×3-days, S.C.). The D1 receptor antagonist, SCH 23390 (0.01, 0.02, 0.07 and 0.1 mg/kg/day×3-days, S.C.), was ineffective in this respect. The results suggest that subchronic apomorphine treatement may induce dopamine D2 receptor sensitization, which in turn reversed amnesia induced by WIN55, 212-2