The reduction in alcohol intake in rats by isoproterenol is attenuated by indomethacin but not enalapril: relationship to blood glucose levels.
Many adrenergic agonists including isoproterenol, a beta1,2-adrenergic agonist, reduce alcohol consumption, but the mechanism of this effect is not known. Adrenergic agonists have a variety of effects, among which are their ability to raise both angiotensin (ANG) II activity and plasma glucose levels. Previous research has shown that ANG II and enhanced glucose levels are accompanied by reductions in alcohol intake. Therefore, the following experiments assessed the roles of each of these factors in the suppression of alcohol intake by isoproterenol. Male Wistar rats were trained to drink a quantity of 6% (w/v) alcohol using the limited access procedure, which offers a daily 40-min access to alcohol and water. In experiment 1, isoproterenol or vehicle was administered s.c. just prior to alcohol availability, and only the group receiving isoproterenol showed a marked reduction in alcohol intake. Following this, the groups were pretreated i.p. with either vehicle or ascending doses of the prostaglandin synthetase inhibitor, indomethacin (2, 4 mg/kg), followed by either isoproterenol or vehicle. Control groups received either two vehicle injections or vehicle and indomethacin. Indomethacin alone did not affect alcohol intake at any of the doses tested but did dose-dependently attenuate the reduction in alcohol intake produced by isoproterenol. In experiment 2, isoproterenol was administered just prior to alcohol availability and when the suppression of alcohol intake stabilized, ascending doses of the angiotensin converting enzyme inhibitor, enalapril (1, 20, 40 mg/kg), were given i.p. 1 h prior to the isoproterenol. Enalapril altered water intake but had no effect on the isoproterenol-induced reduction in alcohol intake. These results show that the inhibition of alcohol drinking by isoproterenol varies more closely with altered glucose levels than with increased ANG II synthesis. They also demonstrate that downstream consequences of a drug may play a role in its effect on alcohol intake.
Biobehavioral Research Department, Addiction Research Foundation of Ontario, University of Toronto, Canada.
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D000428:Alcohol Drinking / Q000188:drug therapy / Q000378:metabolism; D000704:Analysis of Variance; D000804:Angiotensin II / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001786:Blood Glucose; D004326:Drinking; D004656:Enalapril / Q000494:pharmacology*; D000431:Ethanol / Q000008:administration & dosage*; D006943:Hyperglycemia / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology*; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000318:Adrenergic beta-Agonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001786:Blood Glucose; D000804:Angiotensin II; D000431:Ethanol; D004656:Enalapril; D007545:Isoproterenol; D007213:Indomethacin