Action of the 5-HT2A antagonist amperozide on alcohol-induced poikilothermia in rats.

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.