Behavioral effects of the inhibitors of phenylethanolamine-N-methyltransferase, LY 78335 and LY 134046, and their interactions with ethanol.
The centrally active inhibitors of phenylethanolamine-N-methyltransferase (PNMT), LY 78335 and LY 134046, were investigated both alone and in combination with ethanol (2 g/kg) in a holeboard test of directed exploration and locomotor activity. Both PNMT inhibitors showed dose-related reductions in exploratory head-dipping but were without effect on locomotor activity. In combination with ethanol both PNMT inhibitors tended to attenuate the ethanol-induced reductions in exploratory head-dipping but did not effect ethanol's locomotor stimulant properties. LY 134046 showed neither an anxiolytic nor an anxiogenic profile in the plus-maze test of anxiety, nor did it alter the anxiolytic effects of either 1.2 g/kg or 2 g/kg ethanol. LY 134046 did, however, attenuate the ataxic effects of a 2.4 g/kg dose of ethanol. These results may suggest a role for adrenaline synthesis in some, but not all, of the behavioral effects of ethanol.
Durcan
M J
MJ
Laboratory of Clinical Studies, DICBR, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892.
Lister
R G
RG
Linnoila
M
M
D000818:Animals; D001259:Ataxia / Q000139:chemically induced / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology*; D001596:Benzylamines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005106:Exploratory Behavior; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010625:Phenylethanolamine N-Methyltransferase / Q000037:antagonists & inhibitors*
D001552:Benzazepines; D001596:Benzylamines; C002569:2,3-dichloro-alpha-methylbenzylamine; D000431:Ethanol; C028625:LY 134046; D010625:Phenylethanolamine N-Methyltransferase