Possible involvement of brain somatostatin in the memory formation of rats and the cognitive enhancing action of FR121196 in passive avoidance task

Abstract

Using the passive avoidance learning task in rats, the role of brain somatostatin in cognitive function was investigated with special reference to that of the brain cholinergic system. In addition, the involvement of both the brain somatostatinergic and cholinergic systems in the anti-amnesic action of a newly introduced cognitive enhancer, FR121196 [N-(4-acetyl-1-piperazinyl)-4-fluorobenzenesulfonamide], was examined. Treatment with cysteamine (50, 100, 200 mg/kg, s.c.), a depletor of somatostatin, significantly and dose-dependently reduced the retention of single trial passive avoidance task. Similar memory impairments were found in rats which received central cholinergic blockade either by scopolamine (0.1–1 mg/kg) or by lesioning of the nucleus basalis magnocellularis (NBM). Intracerebroventricurally (i.c.v.) administered somatostatin (1–14) (10–1000 ng/rat) significantly ameliorated the memory impairments induced not only by cysteamine (200 mg/kg) but also by scopolamine (1 mg/kg) and NBM-lesioning. Although physostigmine (0.01–1 mg/kg) also ameliorated the memory impairments induced by cysteamine and scopolamine, it failed to affect the memory impairment seen in the NBM-lesioned rats. Administration of FR121196 (0.1–10 mg/kg) significantly ameliorated the memory deficits produced by scopolamine and NBM lesioning but not that induced by cysteamine. Neurochemical examinations showed that administration of cysteamine significantly reduced the contents of somatostatin but not the choline acetyltransferase activities in all the brain areas examined. These results suggest that the brain somatostatin plays an important role in the cognitive function of rats, and appears to be involved in the cognitive enhancing action of FR121196. Furthermore, the cholinergic neurons degenerated by NBM-lesion may be necessary for the memory enhancement by physostigmine but not for that by somatostatin or FR121196.