اثر سيستم كانابينوئيدي ناحيه CA1 هيپوكامپ بر حافظه موش هاي صحرايي حساس شده با آپومرفين

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

Objective: 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. Method: 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. Results: Post-training intra-CA1 infusions of the non-selective CB1-CB2 receptor agonist, WIN55, 212-2 (0.1, 0.25 and 0.5 pg/rat), dose-dependently shortened the step-through latency, suggesting impaired memory retrieval, whereas post-training intra-CA1 micro­injections 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 pg/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/dayx3-days, S.C.), administered 30 min before each injection of apomorphine (0.5 mg/kg/dayx3-days, S.C.). The D1 receptor antagonist, SCH 23390 (0.01, 0.02, 0.07 and 0.1 mg/kg/dayx3-days, S.C.), was ineffective in this respect. Conclusion: The results suggest that subchronic apomorphine treatement may induce dopamine D2 receptor sensitization, which in turn reversed amnesia induced by WIN55, 212-2.