5-HT(1A) receptor antagonist p-MPPI attenuates acute ethanol effects in mice and rats.
The effect of a selective 5-HT(1A) antagonist, 4-(2'-methoxy-)phenyl-1-[2'-(N-2"-pyridinyl)-p-iodobenzamino-]ethyl-piperazine (p-MPPI), on acute ethanol-induced hypothermia, sleep and suppression of acoustic startle reflex in C3H/He mice and Wistar rats was studied. Administration of p-MPPI at the doses of 0.4, 0.7 and 1.0 mg/kg reduced in a dose-dependent manner the ethanol-induced hypothermia and the sleep time and attenuated the ethanol-induced decrease of acoustic startle reflex magnitude in mice. Similar p-MPPI (0.4 mg/kg) effects on ethanol-induced sleep and hypothermia were obtained in rats. It was concluded that 5-HT(1A) receptors were involved in the mechanisms of the ethanol-induced hypothermia and sleep, and that 5-HT(1A) antagonist increased acute ethanol tolerance.
Popova
Nina K
NK
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Lavrentyeva 10, 630090 Novosibirsk, Russia. npopova@bionet.nsc.ru
Ivanova
Elena A
EA
D000208:Acute Disease; D020268:Alcohol-Induced Disorders, Nervous System / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D004361:Drug Tolerance / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D007035:Hypothermia / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects / Q000502:physiology
D000631:Aminopyridines; D010879:Piperazines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; C087205:4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine; D012701:Serotonin; D000431:Ethanol