Losartan improves the performance of ethanol-intoxicated rats in an eight-arm radial maze.
Results of previous research demonstrate that angiotensin II (Ang II) inhibits long-term potentiation (LTP) in medial perforant path-dentate gyrus granule cells and that the inhibition is mediated by the AT1 receptor because it can be blocked by losartan, a specific AT1 receptor antagonist. Ang II impairment of retention and ethanol inhibition of LTP can both be blocked by pretreatment with losartan. Because losartan pretreatment also prevents ethanol intoxication measured in terms of the aerial righting reflex, the purpose of the present study was to assess the effects of 2.0 g/kg ethanol administered by gavage on performance in an eight-arm radial maze, and then to determine the effectiveness of losartan in reducing the impairment of the learning and memory process. Results confirmed the general hypothesis that ethanol-induced cognitive deficits are mediated by Ang II and the AT1 receptor and that the impairment can be reduced by pretreatment with losartan.
Tracy
H A
HA
Division of Life Sciences, University of Texas at San Antonio 78249-0662, USA.
Wayner
M J
MJ
Armstrong
D L
DL
D000435:Alcoholic Intoxication / Q000503:physiopathology / Q000517:prevention & control*; D000804:Angiotensin II / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects*; D007858:Learning / Q000187:drug effects; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008568:Memory / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000431:Ethanol; D019808:Losartan