Abstract

Spatial learnin g is a m odel of hig her human cognitiv e functi ons which is used for studying anim al beh avior. Histaminergic and noradrenergic systems play a modulatory role in learning and memory. The present study ai m ed to tes t th e ef fe ct s of α -a dr e no cep to r a go nis t/ ant ag on ist mi cr oin je ct ion int o th e CA1 re gio n of do rs al hippocampus on histamine-induced spatial learning facilitation in the water maze task. Pre-training intra-CA1 microinjection of α 1 -or α 2 -adrenergic agonist, phenylephrine (0.0025 μg/rat) or clonidine (0.05μ g/rat) de-creased traveled distance and escape latency at the start of the training phase, suggesting a spatial learning facil-itation; 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 -r eceptor a ntagonist, pr azosin (1 μg/rat) impaired spatial l earning; α2 -r ec ep t o r a nt ag o n i s t , y o hi m b i n e (0.25 μg/rat) fa cilitated spatial acquisition. Moreover, pre-tra in in g in t ra- C A1 micro in j ec tion of a sub thresh old d ose of phenyl ephrin e ( 0.001 μg/rat) reversed histamine r esponse, while i neff ective dose co-administration of clonidine (0.1 μg/rat) potentiated h is tamine (0.01 μg/rat) r es p onse. S ubthr es hold d ose o f p ra zosin or yohimbine did n ot alter hist am ine respo nse. B ilat e ra l i nfu sio n of h istamine (0. 05 μg/ rat) facilit ated spati al l ea rning by i tself. Fu rt hermore, 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 s patial acquis ition.