Relationship of the effects of the benzodiazepine derivative clorazepate on corticosterone secretion with its behavioural actions. Antagonism by Ro 15-1788.
The effectiveness of Ro 15-1788, a benzodiazepine receptor antagonist, in modifying the effects of the benzodiazepine derivative clorazepate on schedule-controlled behaviour and pituitary-adrenal activity of rats was investigated. At low doses (5 mg/kg) clorazepate increased punished responding and slightly decreased basal plasma corticosterone levels. At high doses (40 mg/kg), clorazepate suppressed fixed ratio responding, raised basal plasma levels of corticosterone and reduced the stress response produced by exposure to a novel environment. Pretreatment with Ro 15-1788 blocked the behavioural and neuroendocrine effects of the high dose of clorazepate. These results suggest that both types of effects of clorazepate share a common mechanism which involves brain benzodiazepine receptors.
D000302:Adrenal Cortex / Q000378:metabolism; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D003009:Clorazepate Dipotassium / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D003345:Corticosterone / Q000378:metabolism*; D005442:Flumazenil; D006801:Humans; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D013315:Stress, Psychological / Q000097:blood / Q000188:drug therapy*
D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D011963:Receptors, GABA-A; D005442:Flumazenil; D003009:Clorazepate Dipotassium; D003345:Corticosterone