Ethanol-induced suppression of LTP can be attenuated with an angiotensin IV analog.
Hippocampal slices taken from animals chronically or acutely treated with ethanol exhibit significant inhibition of long-term potentiation (LTP). This inhibition appears to be associated with impaired activity of N-methyl-D-aspartate (NMDA) receptors, perhaps via ethanol-induced increases in GABAergic synaptic transmission. Recently, a role for the octapeptide angiotensin II (AngII) in ethanol's inhibition of LTP has been reported. Complementary to these findings our laboratory has shown that the application of the hexapeptide metabolite of AngII, angiotensin IV (AngIV), significantly facilitated normal tetanic-induced LTP in the hippocampal slice. This facilitation is presumably by activation of the angiotensin receptor subtype, AT(4). The present study tested whether an AT(4) receptor agonist could overcome ethanol-induced suppression of LTP. The results indicate that Nle(1)-AngIV could offset ethanol-induced suppression of LTP in the CA(1) region of the hippocampus. Pretreatment with the specific AT(4) receptor antagonist Nle(1), Leual(3)-AngIV blocked this facilitation implicating the involvement of the AT(4) receptor subtype. These results suggest that an AT(4) receptor agonist is effective in overcoming ethanol's suppressing influence on LTP, and encourage further investigation of the cognitive enhancing properties of such compounds.
Wright
John W
JW
Department of Psychology, Washington State University, Pullman, WA 99164-4820, USA. wrightjw@wsu.edu
Kramár
Enikö A
EA
Myers
Elizabeth D T
ED
Davis
Christopher J
CJ
Harding
Joseph W
JW
D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D002492:Central Nervous System Depressants; C118983:Nle(1)-AngIV; D009842:Oligopeptides; D016194:Receptors, N-Methyl-D-Aspartate; D000804:Angiotensin II; D000431:Ethanol