Attenuation of the discriminative stimulus properties of ethanol and oxazepam, but not of pentobarbital, by Ro 15-4513 in mice.
The imidazobenzodiazepine Ro 15-4513 has a high affinity for central benzodiazepine binding sites and has been shown to antagonize certain effects of ethanol. The purpose of the present study was to determine if Ro 15-4513 would attenuate the discriminative stimulus properties of ethanol and the other central nervous system depressants pentobarbital and oxazepam. Different groups of mice were trained to discriminate 1.0 or 1.5 g/kg of ethanol, 20 mg/kg of pentobarbital or 10 mg/kg of oxazepam from saline injections in a two-lever operant task. Stimulus generalization tests were conducted with Ro 15-4513 alone (0.01-20 mg/kg) and in combination with the training drugs. The discriminative stimulus effects of ethanol and oxazepam, but not of pentobarbital, were blocked by Ro 15-4513. When given alone in each of the different drug-training groups, Ro 15-4513 did not produce drug-lever responding but decreased overall response rates in a dose-related fashion. Although the alcohols, barbiturates and benzodiazepines share discriminative stimulus properties under many conditions, the selective blockade of their stimulus effects provides further evidence that their actions may be mediated by different cellular mechanisms. These data also show that Ro 15-4513 may attenuate behavioral effects of ethanol relevant to its abuse.
Rees
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Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Balster
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D000818:Animals; D001386:Azides / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005795:Generalization, Stimulus / Q000187:drug effects*; D008297:Male; D051379:Mice; D010076:Oxazepam / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects
D001386:Azides; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D000431:Ethanol; D010076:Oxazepam; C042957:Ro 15-4513; D010634:Phenobarbital