ROLE OF 5-HT4 RECEPTORS IN THE MOUSE PASSIVE-AVOIDANCE TEST

The effects of the administration of different 5-HT4 receptor antagoni sts (SDZ 205557, GR 125487) and 5-HT4 receptor agonists (BIMU 1, BIMU 8) on memory processes were evaluated in the mouse passive avoidance t est. The administration of SDZ 205557 (10 mg kg(-1) i.p.) and GR 12548 7 (10 mg kg(-1) i.p.) immediately after termination of the training se ssion produced an amnesic effect. BIMU 1 (20 mg kg(-1) i.p.) and BIMU 8 (30 mg kg(-1) i.p.), administered 20 min before the training session , prevented the 5-HT4 receptor antagonist-induced amnesia. In the same experimental conditions BIMU 1 (10 mg kg(-1) i.p.; 25 mu g/mouse intr acerebroventricularly) and BIMU 8 (30 mg kg(-1) i.p.; 30 mu g per mous e intracerebroventricularly) prevented scopolamine (1 mg kg(-1) i.p.) and dicyclomine (2 mg kg(-1) i.p.) amnesia and, at the dose of 10 and 30 mg kg(-1) i.p. respectively, prevented amnesia induced by exposure to a hypoxic environment. At the highest effective doses, none of the drugs impaired motor coordination, as revealed by the rota rod test, o r modified spontaneous motility and inspection activity, as revealed b y the hole board and Animex tests. The 5-HT3 antagonist ondansetron (0 .1-1 mg kg(-1) i.p.) was unable to prevent scopolamine-, 5-HT4 antagon ist- and hypoxia-induced amnesia. These results suggest that the modul ation of 5-HT4 receptors plays an important role in the regulation of memory processes. On these bases, the 5-HT4 receptor agonists could be useful in the treatment of cognitive deficits although 5-HT4 receptor antagonists may represent pharmacological tools for investigation of new potential antiamnesic drugs.