Differential effects of Ro15-1788 in actions of chlordiazepoxide and ethanol.
Three behavioral tests, namely, runway activity, horizontal dowel test and hypothermia, were used to compare the effects of Ro15-1788, a specific benzodiazepine antagonist, on the common neuropharmacological actions of chlordiazepoxide (CDP) and ethanol in C57BL/6J mice. Ro15-1788 completely reversed the CDP-induced inhibition of runway activity and incoordination on a horizontal dowel, but only partially antagonized the hypothermic effects of CDP. The latter phenomenon was likely to be due to the rapid elimination of Ro15-1788, but could also be due to the fact that hypothermia might not be a specific action of CDP. The sedative actions of ethanol were not antagonized at all by Ro15-1788. In fact, Ro15-1788 potentiated the incoordinating effect of ethanol as determined by the horizontal dowel test such that mice injected with Ro15-1788/ethanol had lower brain ethanol levels than mice injected with vehicle/ethanol when they fell off the dowel. In contrast, mice injected with Ro15-1788/CDP took longer to fall off and had significantly higher CDP levels at fall-off than mice injected with vehicle/CDP. The stimulatory effect of a low dose of ethanol on runway activity was reversed by Ro15-1788. These data are discussed in terms of the possible mechanisms of actions for CDP and ethanol.
Chan
A W
AW
Research Institute on Alcoholism, New York State Division of Alcoholism and Alcohol Abuse, Buffalo 14203.
Langan
M C
MC
Schanley
D L
DL
Penetrante
M L
ML
Leong
F W
FW
Aldrich-Castanik
L
L
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D002707:Chlordiazepoxide / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004347:Drug Interactions; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000633:toxicity; D005442:Flumazenil / Q000494:pharmacology*; D007035:Hypothermia / Q000139:chemically induced; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology
D011963:Receptors, GABA-A; D000431:Ethanol; D005442:Flumazenil; D002707:Chlordiazepoxide