Effects of the imidazobenzodiazepine RO15-4513 on the stimulant and depressant actions of ethanol on spontaneous locomotor activity.
The purpose of this study was to investigate the effects of the imidazobenzodiazepine RO15-4513, a partial inverse agonist at benzodiazepine (BDZ) receptors, on the stimulant and depressant actions of ethanol in mice. For comparative purposes, another BDZ inverse agonist, FG-7142, was examined as well. Neither RO15-4513 nor FG-7142 influenced the low-dose excitatory effects of ethanol on spontaneous locomotor activity. However, both RO15-4513 and FG-7142 significantly antagonized the depressant effects of ethanol, and this antagonism was completely reversed by pretreatment with the BDZ receptor antagonist, RO15-1788. These data suggest that RO15-4513 is capable of antagonizing only some of the behavioral effects of ethanol, and in particular, those responses to ethanol that are mediated by modulation of the GABA/BDZ-chloride channel receptor complex.
Becker
H C
HC
Veterans Administration Medical Center, Charleston, SC.
D000818:Animals; D001386:Azides / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D002243:Carbolines / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005442:Flumazenil / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009043:Motor Activity / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology
D001386:Azides; D002243:Carbolines; D002712:Chlorides; D007473:Ion Channels; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D000431:Ethanol; D005442:Flumazenil; C035874:FG 7142; C042957:Ro 15-4513