Histaminergic activation of endogenous angiotensin II fails to inhibit alcohol intake in rats

Demonstrations that alcohol intake can be inhibited by pharmacological activation of the renal renin-angiotensin system (RRA) or injection of angiotensin II (ANG II) in rats led to this study of a role for endogenous ANG II in inhibition of alcohol intake in rats. Relatively small doses of histamine, above threshold for eliciting drinking of water and activation of the RRA, were injected SC in adult male Sprague-Dawley rats with access to 3.0% alcohol in 45-min one-bottle alcohol tests and in two-bottle tests in which alcohol and water were available at the midpoint of the 12-h dark phase. The 0.312 and 1.25 mg/kg doses of SC histamine elevated plasma renin activity to levels similar to those in rats that had just eaten food. Neither dose of histamine affected alcohol intake in one-bottle tests. A relatively large 10 mg/kg dose of histamine increased alcohol intake in a one-bottle test, but decreased alcohol intake and increased water intake in two-bottle tests. The inhibitory effect of the 10 mg/kg dose of histamine on alcohol intake was completely blocked by SC 10 mg/kg losartan, a selective AT1 angiotensin receptor antagonist. This 10 mg/kg dose of losartan given alone, however, failed to increase alcohol intake in one- or two-bottle tests. These results generally do not support a role for endogenous ANG II as an inhibitory physiological signal in the control of alcohol ingestion in rats, because histaminergic activation of RRA, using small but physiologically meaningful doses of histamine, failed to inhibit alcohol intake.