Neurotensin attenuates the reduction in alcohol drinking produced by angiotensin II

Neurotensin enhances some of the behavioral effects of alcohol including motor impairment, narcosis, hypothermia and also interacts with some of the physiological actions of angiotensin (ANG) II including aldosterone release and increased blood pressure. ANG II injections also produce a dose-dependent antagonist reversible reduction in alcohol drinking. The present study is the first to examine the interaction between neurotensin and angiotensin in the behavioral context of oral alcohol self-administration. Adult male Wistar rats acquired alcohol drinking (6% w/v) using the limited access procedure which makes alcohol available for 40 min every day. When intake stabilized ANG II (400 micrograms/kg per day) or vehicle were administered subcutaneously (SC) just prior to alcohol availability but only the group receiving ANG II showed a marked reduction in alcohol intake. Following this the groups were pretreated sc with either vehicle or ascending doses of neurotensin (5, 10, 20 micrograms/kg) followed by either ANG II or vehicle. Control groups received either two vehicle injections or vehicle and neurotensin injection. Neurotensin alone did not affect alcohol intake at any of the doses tested but did attenuate, in a dose-dependent fashion, the reduction in alcohol intake produced by ANG II. These results demonstrate neurotensin's ability to alter the behavioral effect of ANG II on alcohol intake.