Semenova T P, Ticku M K
Department of Pharmacology, University of Texas Health Science Center, San Antonio 78284-7764.
Brain Res. 1992 Aug 21;588(2):229-36. doi: 10.1016/0006-8993(92)91580-8.
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.
研究了5-羟色胺（5-HT）受体亚型和α2-肾上腺素能受体拮抗剂对DBA/2小鼠听源性惊厥和运动活性的影响。5-HT1c受体拮抗剂（米安色林和赛庚啶）、5-HT3受体拮抗剂（扎考必利）和5-HT4受体拮抗剂（ICS 205-930）可延长幼龄（20-27日龄）DBA/2小鼠听源性惊厥的潜伏期，并减轻惊厥的严重程度。然而，这些拮抗剂在老龄（30-37日龄）小鼠中的作用有所不同。5-HT2受体拮抗剂酮色林对听源性惊厥无任何作用。α2-肾上腺素能受体拮抗剂育亨宾（0.5mg/kg，腹腔注射）可加重听源性惊厥的严重程度，且在育亨宾存在的情况下，5-HT受体亚型拮抗剂的抗惊厥作用更为明显。5-HT3和5-HT4受体拮抗剂可使幼龄小鼠产生运动活性降低，而5-HT1c和5-HT2受体拮抗剂对运动活性无任何影响。育亨宾对运动活性无诱导作用，但在育亨宾存在的情况下，给予5-HT3、5-HT4和5-HT1c受体拮抗剂后，小鼠表现出更明显的运动活性降低。然而，在老龄小鼠中，这些药物的结果有所不同。这些观察结果表明5-HT1c、5-HT3、5-HT4和α2-肾上腺素能受体在幼龄DBA/2小鼠听源性惊厥中起作用，5-HT3和5-HT4受体在这些小鼠的运动活性中起作用。此外，这些结果还提示5-HT受体与α2-肾上腺素能受体之间存在相互作用，以及中枢神经系统中各种5-HT受体亚型的不同发育模式。
