Hippocampal α-adrenoceptors involve in the effect of histamine on spatial learning

Spatial learning is a model of higher human cognitive functions which is used for studying animal behavior. Histaminergic and noradrenergic systems play a modulatory role in learning and memory. The present study aimed to test the effects of α-adrenoceptor agonist/antagonist microinjection into the CA1 region of dorsal hippocampus on histamine-induced spatial learning facilitation in the water maze task. Pre-training intra-CA1 microinjection of α1- or α2-adrenergic agonist, phenylephrine (0.0025 μg/rat) or clonidine (0.05 μg/rat) decreased traveled distance and escape latency at the start of the training phase, suggesting a spatial learning facilitation; while the higher dose of the drugs (phenylephrine 0.005 μg/rat, clonidine 0.2 and 0.5 μg/rat) increased the performance level at the end of the training phase, indicating a water maze spatial acquisition impairment. However, α1-receptor antagonist, prazosin (1 μg/rat) impaired spatial learning; α2-receptor antagonist, yohimbine (0.25 μg/rat) facilitated spatial acquisition. Moreover, pre-training intra-CA1 microinjection of a subthreshold dose of phenylephrine (0.001 μg/rat) reversed histamine response, while ineffective dose co-administration of clonidine (0.1 μg/rat) potentiated histamine (0.01 μg/rat) response. Subthreshold dose of prazosin or yohimbine did not alter histamine response. Bilateral infusion of histamine (0.05 μg/rat) facilitated spatial learning by itself. Furthermore, the drug's injections had no effect on swimming speed on the training days of MWM. These results suggest that α-adrenergic receptors of the dorsal hippocampal CA1 regions may play an important role in histamine-induced facilitation of spatial acquisition.