DAU 6215, a novel 5-HT3-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 micrograms 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 micrograms 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.
Brambilla
A
A
Department of Pharmacology, Boehringer Ingelheim Italia S.p.A., Milano.
Ghiorzi
A
A
Pitsikas
N
N
Borsini
F
F
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*
D001562:Benzimidazoles; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D012702:Serotonin Antagonists; C070191:itasetron; D012601:Scopolamine