Attenuation of the behavioural effects of ethanol in mice by des-enkephalin-gamma-endorphin (ORG 5878).
This study shows inhibition of the increase in locomotor activity induced by ethanol (2 g/kg i.p.) in mice by a low dose (0.1 mg/kg i.p.) of the non-opioid beta-endorphin fragment ORG 5878 (des-enkephalin-gamma-endorphin). ORG 5878 (0.1 mg/kg i.p.) also significantly antagonised the large increase in electroshock seizure threshold produced by ethanol (1.5 g/kg i.p.). In contrast, the hypothermia induced by ethanol (2 g/kg i.p.) was not altered by ORG 5878 (0.1 mg/kg i.p.). The effects of ORG 5878 showed an abnormal dose-response relationship, in that a high dose (1 mg/kg i.p.) did not significantly suppress any of the behavioural effects of ethanol examined although there was some indication that it attenuated the stimulant action of ethanol. ORG 5878 (0.1, 1 mg/kg i.p.) did not have any intrinsic effects on locomotion, seizure threshold or body temperature in mice. These results are the first demonstration that ORG 5878 may act as an ethanol antagonist in some paradigms.
Jackson
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HC
Reckitt & Colman Psychopharmacology Unit, Department of Pharmacology, School of Medical Sciences, University Walk, Bristol, U.K.
Ramsay
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E
Nutt
D J
DJ
D000818:Animals; D001143:Arousal / Q000187:drug effects*; D001833:Body Temperature Regulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007696:Kindling, Neurologic / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D012684:Sensory Thresholds / Q000187:drug effects; D001615:beta-Endorphin / Q000494:pharmacology*
D000431:Ethanol; D001615:beta-Endorphin; C033558:des-enkephalin-gamma-endorphin