Angiotensin AII AT1 receptor mediates ethanol-diazepam inhibition of hippocampal LTP.
Within a limited range of doses, co-administration of ethanol (EtOH) and diazepam (DZ) produce enhanced anxiolytic effects. These combined effects on long-term potentiation (LTP) in the hippocampus of rats anesthetized with urethane were studied in an attempt to provide an explanation at a more fundamental neuronal level. Male Sprague-Dawley rats received 0.1, 0.5, 0.75 and 1.0 mg/kg DZ i.p. in combination with 0.1, 0.5, 0.75 g and 1.0 g/kg EtOH by gavage, respectively. Drugs were administered 20 min (EtOH) and 15 min (DZ) prior to tetanic stimulation of the medial perforant path which resulted in LTP induction measured in terms of the relative change in amplitude of the population EPSP as compared to baseline. Effects of both drugs alone and in combination on LTP are presented. Both drugs depressed LTP induction and significant enhanced interactive effects were observed. We have previously shown that angiotensin II (AII) inhibits LTP induction and that the inhibition can be blocked by losartan, an AII AT1 receptor antagonist. Our present results demonstrate that the combined inhibitory effects of EtOH and DZ on LTP induction are also blocked by losartan.
Wayner
M J
MJ
Division of Life Sciences, University of Texas at San Antonio 78249-0662.
Polan-Curtain
J
J
Armstrong
D L
DL
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D003975:Diazepam / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects*; D019808:Losartan; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology
D001713:Biphenyl Compounds; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D000431:Ethanol; D019808:Losartan; D003975:Diazepam