The effect of antagonists of
serotonin (5-HT) receptor subtypes and alpha 2-adrenoceptors was investigated on audiogenic
seizures and locomotor activity in DBA/2 mice. 5HT1c receptor antagonists (
mianserin and
cyproheptadine),
5-HT3 receptor antagonist (
zacopride) and
5-HT4 receptor antagonist (ICS 205-930) increased the latency of audiogenic
seizures and decreased the severity of convulsions in young (20-27 days old) DBA/2 mice. However, the effect of these antagonists varied in older (30-37 days old) mice.
Ketanserin, 5-HT2 receptor antagonist, was devoid of any activity on audiogenic
seizures.
Yohimbine (0.5 mg/kg, i.p.), an alpha 2-adrenoceptor antagonist, increased the severity of audiogenic
seizures, and the anti-
convulsant effect of
5-HT receptor subtypes antagonists became more pronounced in the presence of
yohimbine. 5-HT3 and
5-HT4 receptor antagonists produced hypolocomotor activity in young mice whereas 5-HT1c and 5-HT2 receptor antagonists were devoid of any effect on locomotor activity.
Yohimbine did not induce any effect on locomotor activity but the mice exhibited more pronounced hypolocomotor activity following the administration of 5-HT3, 5-HT4 and 5HT1c receptor antagonists in the presence of
yohimbine. However, the results varied with these agents in the older mice. These observations implicate a role of 5-HT1c, 5-HT3, 5-HT4 and alpha 2-adrenoceptors in audiogenic
seizures in young DBA/2 mice, and 5-HT3 and 5-HT4 receptors in locomotor activity in these mice. Furthermore, these results also suggest an interaction between
5-HT receptors and alpha 2-adrenoceptors, and differential development patterns of various
5-HT receptor subtypes in the CNS.