Is inhibition by diazepam and beta-carbolines of estrogen-induced luteinizing hormone secretion related to sedative effects?
The effects of diazepam (DZ) and the beta-carbolines ZK-91296 and ZK-93423 on luteinizing hormone (LH) release evoked by beta-estradiol were studied in estradiol-primed ovariectomized rats. Acute treatment with 2.5, 5 and 10 mg/kg DZ and ZK-91296 significantly blunted the LH response. ZK-93423 (1, 5 and 10 mg/kg) produced a similar effect. The inverse agonist DMCM (2 mg/kg) was unable to modify plasma LH levels in estrogen-primed, ovariectomized rats. Sedative effects were observed with doses of DZ (1 mg/kg) ineffective to blunt the LH response. In contrast, ZK-91296 (5 mg/kg) produced inhibition of LH surges in nonsedative doses. These results indicate that diazepam and beta-carboline agonists prevent the LH surge evoked by estrogen. They suggest, in addition, that the actions on LH release and their sedative effects are not directly related.
Laboratorio de Investigaciones Cerebrales, Facultad de Ciencias Medicas, Universidad Nacional de Cuyo, Mendoza, Argentina.
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Gargiulo
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Donoso
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D010052:Ovariectomy; D051381:Rats; D011919:Rats, Inbred Strains
D014151:Anti-Anxiety Agents; D002243:Carbolines; D004965:Estrogen Antagonists; D006993:Hypnotics and Sedatives; C038933:ZK 91296; D007986:Luteinizing Hormone; D003975:Diazepam