Abstract

The effects of the administration of different 5-HT₄receptor antagonists (SDZ 205557, GR 125487) and 5-HT₄receptor agonists (BIMU 1, BIMU 8) on memory processes were evaluated in the mouse passive avoidance test. The administration of SDZ 205557 (10 mg kg⁻¹ i.p.) and GR 125487 (10 mg kg⁻¹i.p.) immediately after termination of the training session 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 μg/mouse intracerebroventricularly) and BIMU 8 (30 mg kg⁻¹ i.p.; 30 μg per mouse 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, or modified spontaneous motility and inspection activity, as revealed by 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 antagonist- and hypoxia-induced amnesia. These results suggest that the modulation 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.