Myers R D, Lankford M
Department of Pharmacology School of Medicine, East Carolina University, Greenville, NC 27858, USA.
Pharmacol Biochem Behav. 1998 Jan;59(1):91-5. doi: 10.1016/s0091-3057(97)00330-4.
Amperozide, a novel 5-HT2A receptor antagonist that releases dopamine from mesolimbic neurons suppresses alcohol drinking in rats. Because serotonergic neurons are implicated in both the central mechanisms underlying thermoregulation and the reinforcing effects of alcohol, this study was undertaken to determine whether the poikilothermic effects of alcohol on body temperature (Tb) would be altered by amperozide. In adult male Sprague-Dawley rats kept at an ambient temperature of 22 to 24 degrees C, a radio transmitter for continuous monitoring of Tb was first implanted intraperitoneally. Then, amperozide was given subcutaneously in a dose of 2.5, 5.0, or 10.0 mg/kg 30 min before an intragastric gavage of either 2.0 g/kg or 4.0 g/kg 20% ethyl alcohol (v/v). Amperozide blocked dose dependently the fall in Tb of the lower 2.0 g/kg dose of alcohol. However, only the higher 5.0 mg/kg and 10.0 mg/kg doses of amperozide prevented the initial thermolytic action of the higher 4.0 g/kg dose of alcohol. Further, the 10.0 mg/kg dose of amperozide given prior to the control saline gavage evoked a hyperthermic response in the rats that persisted for 5 h. These results suggest that the antagonism of 5-HT2A receptors on central serotonergic synapses involved in thermoregulation acts to counteract the potent thermolytic effects of alcohol at an ambient temperature that is below thermoneutrality.
氨哌齐特是一种新型5-羟色胺2A（5-HT2A）受体拮抗剂，可从中脑边缘神经元释放多巴胺，它能抑制大鼠的酒精摄入。由于血清素能神经元与体温调节的中枢机制以及酒精的强化作用均有关联，因此开展了本研究，以确定氨哌齐特是否会改变酒精对体温（Tb）的变温动物效应。在环境温度保持在22至24摄氏度的成年雄性Sprague-Dawley大鼠中，首先经腹腔植入一个用于持续监测Tb的无线电发射器。然后，在经胃管灌喂2.0 g/kg或4.0 g/kg 20%乙醇（v/v）前30分钟，皮下给予2.5、5.0或10.0 mg/kg剂量的氨哌齐特。氨哌齐特剂量依赖性地阻断了较低2.0 g/kg剂量酒精引起的Tb下降。然而，只有较高的5.0 mg/kg和10.0 mg/kg剂量的氨哌齐特能阻止较高4.0 g/kg剂量酒精的初始散热作用。此外，在灌喂对照生理盐水前给予10.0 mg/kg剂量的氨哌齐特，可使大鼠出现持续5小时的体温过高反应。这些结果表明，参与体温调节的中枢血清素能突触上5-HT2A受体的拮抗作用，在低于热中性的环境温度下，可抵消酒精强大的散热作用。
