The reduction in alcohol drinking by peripherally injected angiotensin II is selectively mediated by the AT1 receptor subtype.
We investigated which of the two angiotensin (ANG) receptor subtypes mediates the reduction in alcohol intake produced by peripheral injections of ANG II. Adult male Wistar rats were trained to self-administer alcohol (6% w/v) using a procedure that, by limiting access to a brief daily availability period (40 min), fosters a bout pattern of alcohol drinking and a pharmacodynamic effect. Water was continuously available. Once intake stabilized, groups received daily injections either 200 micrograms/kg ANG II SC or the control vehicle saline immediately prior to alcohol availability. Alcohol consumption was attenuated and water intake elevated in the groups receiving ANG II and was unaffected by the vehicle injections. Following this, different groups were pretreated with ascending doses (0.25, 0.5, 1.0 mg/kg) of either PD123319, the selective AT2 receptor antagonist, Sar1,Thr8-ANG II (0.25 mg/kg), the nonselective ANG II antagonist, or DuP753 (0.25, 0.5, 1.0 mg/kg), the selective AT1 receptor antagonist. Control groups received antagonist pretreatment followed by the ANG II vehicle. Neither PD123319, DuP753, or Sar1, Thr8-ANG II had any effect of their own on alcohol or water intake. Pretreatment with PD123319 did not alter the suppressive effect of ANG II on alcohol intake. DuP753 produced a dose-dependent attenuation in the suppressive effect of ANG II on alcohol intake and antagonized the dipsogenic effect of ANG II on water intake. The effect of Sar1,Thr8-ANG II was similar to that of DuP753. These findings suggest that the reduction in alcohol intake produced by ANG II is mediated through the AT1 receptor subtype.
Grupp
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LA
Primary Mechanisms Department, Addiction Research Foundation of Ontario, Toronto, Canada.
Harding
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D000428:Alcohol Drinking / Q000523:psychology*; D000804:Angiotensin II / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; D019808:Losartan