Involvement of dopaminergic and glutamatergic systems of the basolateral amygdala in amnesia induced by the stimulation of dorsal hippocampal cannabinoid receptors.

The present study intended to investigate the involvement of dopaminergic and glutamatergic systems of the basolateral amygdala in amnesia induced by the stimulation of dorsal hippocampal cannabinoid receptors in male Wistar rats. The animals were stereotaxically implanted with guide cannulas in the CA1 region of the dorsal hippocampus and basolateral amygdala (BLA), trained in a step-through type passive avoidance task, and tested 24 h after training to measure memory retrieval. Post-training intra-CA1 microinjection of the nonselective CB1/CB2 receptor agonist WIN55,212-2 (WIN) (0.1-0.5 μg/rat) dose-dependently induced amnesia. Post-training intra-BLA administration of the D1/D2 dopamine receptor agonist apomorphine (0.3 and 0.5 μg/rat) plus intra-CA1 administration of 0.1 μg/rat of WIN, which alone did not induce amnesia, inhibited memory formation. The inhibitory effect of 0.5 μg/rat of WIN (intra-CA1) on memory formation was significantly decreased by the D1 dopamine receptor antagonist SCH23390 (0.1-0.5 μg/rat, intra-BLA) or the D2 dopamine receptor antagonist sulpiride (0.02-0.5 μg/rat, intra-BLA) given 5 min before post-training intra-CA1 microinjection of WIN. It is important to note that single intra-BLA microinjection of the same doses of apomorphine, SCH23390 or sulpiride had no effect on memory retrieval in passive avoidance task. On the other hand, post-training co-administration of N-methyl-d-aspartate (NMDA; 0.03 and 0.05 μg/rat, intra-BLA) plus an ineffective dose of WIN (0.1 μg/rat, intra-CA1) induced amnesia. Furthermore, the inhibitory effect of 0.5 μg/rat of intra-CA1 microinjection of WIN on memory formation was significantly decreased by pre-treatment with intra-BLA microinjection of the NMDA receptor antagonist d-2-amino-5-phosphonopentanoic acid (d-AP5; 0.1 and 0.5 μg/rat, intra-BLA). Intra-BLA microinjection of the same doses of NMDA or d-AP5 by itself did not induce any response on memory retrieval. Taken together, these findings support the existence of a functional interaction between dorsal hippocampal and basolateral amygdaloid neural circuits during processing cannabinoid-induced amnesia.