Ameliorative effects of histamine on spatial memory deficits induced by scopolamine infusion into bilateral dorsal or ventral hippocampus as evaluated by the radial arm maze task.

1. The present study examined the role of the hippocampal histaminergic system in the regulation of spatial memory deficit in rats using the radial arm maze task after scopolamine injection into the bilateral dorsal (DH) or ventral (VH) hippocampus. 2. Bilateral injection of scopolamine (5 microg/site) into both the DH and VH impaired spatial memory in the retrieval memory process. Injection of histamine (50 or 100 ng/site) in the DH and intraperitoneal injection of histidine (100 mg/kg) markedly improved working memory and reference memory deficits induced by scopolamine injection into the DH. The histamine H(1) receptor antagonist pyrilamine (1 microg/site) abolished the ameliorative effects of histidine on working memory deficits, whereas both pyrilamine and the H(2) receptor antagonist cimetidine (0.5 microg/site) abolished the effect of histidine on reference memory. 3. Local injection of histamine (25 or 50 ng/site) into the VH and systemic injection of histidine (50 or 100 mg/kg) markedly improved working memory deficits induced by scopolamine injection into the VH, but did not improve the deficits in reference memory. Injection of both pyrilamine (0.2, 0.5 and 1 microg/site) and cimetidine (0.1 and 0.5 microg/site) into the VH reversed the effects of histidine. 4. The results of the present study indicate that histamine has different actions on cholinergic-related memory in the the DH and VH. Histamine in the DH ameliorates spatial working memory deficits by acting on histamine H(1) receptors and reference memory deficits through both H(1) and H(2) receptors. However, histamine in the VH ameliorates working memory deficits via an action on both H(1) and H(2) receptors.