Role of angiotensin II and the subfornical organ in the pharmacological actions of ethanol.

Abstract

The current study was designed to evaluate if angiotensin II mediates the hypothermic effects of ethanol, and to determine if the effects of angiotensin are mediated centrally. We also tested the hypothesis that the subfornical organ (SFO) is a site responsible for the alterations in body temperature and aerial righting reflex mediated by ethanol and for the modulation of ethanol consumption in rats. Male Sprague-Dawley rats were used in a series of experiments to evaluate the role of both peripheral and central administration of losartan, a selective angiotensin type 1 receptor antagonist on ethanol-induced hypothermia. Subsequent studies were undertaken in SFO-lesioned rats to evaluate the effects of SFO-lesion on alcohol intake, the thermal response to alcohol and angiotensin, and the aerial righting reflex. Selective antagonism of the angiotensin II type 1 receptor, administered either peripherally or centrally, attenuated not only the fall in colonic temperature but also attenuated the transient rise in tail skin temperature that was associated with administration of ethanol. The thermal responses to both angiotensin and ethanol were similarly attenuated in SFO-lesioned rats. Likewise the aerial righting reflex, which has previously been shown to be impaired by losartan treatment, was also significantly attenuated in SFO-lesioned animals. Alcohol intake, as determined by a 48 h, two-bottle preference test also revealed that SFO-lesioned animals consumed significantly less alcohol (ethanolic beer) than did controls. Collectively, the results demonstrate that ethanol-induced temperature responses are mediated by the renin-angiotensin system and that this interaction is mediated centrally. In addition, the results demonstrate that the SFO is a site that mediates several neurobiological effects of ethanol, possibly via the renin-angiotensin system.