DAU-6215, A NOVEL 5-HT(3)-RECEPTOR ANTAGONIST, SELECTIVELY ANTAGONIZES SCOPOLAMINE-INDUCED DEFICIT IN A PASSIVE-AVOIDANCE TASK, BUT NOT SCOPOLAMINE-INDUCED HYPERMOTILITY IN RATS

This study examined the effects of DAU 6215, a selective 5-HT3-receptor antagonist, on either impairment of a passive-avoidance task or hypermotility, both caused by scopolamine in rats. In the first experiment, scopolamine (0.75 mg kg-1, i.p.) disrupted acquisition of a one-trial 'step through' passive-avoidance response. Pretreatment with DAU 6215 (1, 10, 30 and 100 mug kg 1, i.p.) antagonized this deficit induced by scopolamine, with a bell-shaped dose-response curve. Scopolamine (0.75 mg kg 1, i.p.) produced a significant increase in locomotor activity which was unaffected by pretreatment with DAU 6215 (10 and 30 mug kg-1, i.p.). The present results further support the suggestion that 5-HT3-receptor antagonists may prevent the memory disturbance caused by a reduction in central cholinergic function in the rat. The inefficacy shown by DAU 6215 on hyperactivity induced by scopolamine appears to rule out the possibility of a pharmacokinetic interference between DAU 6215 and scopolamine.