Abstract

Several types of learning and memory processes are regulated by the hippocampus which is an important subcortical structure in the mammalians' brain. Previous investigations have shown that different receptor systems in the CA1 regio n of hippocampus are invol ved in learning and memory functions. Investigating the possible in fl uence of dorsal hippocampal GABA- A receptors on histamine-induced spatial facilitation in adult male Wistar rats was the focus of the current study. Rats were bilaterally implanted with dorsal hippo-campal (CA1) cannulae, recovered from surgery and then trained in Morris water maze (MWM) for 4 consec-utive days. A block of four trials was given each day. All drugs were injected into CA1 regions, 5 min before training. Pre-training intra-CA1 microinjection of muscimol, a GABA-A receptor agonist, at the dose of 0.01 or 0.02μg/rat, increased the traveled distance or the escape latency and traveled distance to the hidden plat-form, respectively, indicating a water maze spatial acquisition impairment. Intra-CA1 administration of bicuculline, a GABA-A receptor antagonist however, signifi cantly decreased the escape latency and traveled distance to the hidden platform, suggesting a spatial learning facilitation . On the other hand, pre-training intra-CA1 m icroinjection of the subthreshold dose of muscimol plus differe nt doses of histamine (0.025, 0.05 and 0.1 μ g/rat) did not alter the histamine response. Meanwhile, the co-administration of the ineffective dose of bicuculline together with histamine potentiated the spatial learning. Moreover, bilateral infusion of histamine (0.025, 0.05 and 0.1μg/rat) by itself, facilitated the spatial learning. Notably, the drug injections had no effect on swimming speed during the MWM training sessions. Our results suggest that the dorsal hippo-campal (CA1) GABA-A mechanism(s) may influence the histamine-induced facilitation of spatial acquisition