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.
Gargiulo
P A
PA
Laboratorio de Investigaciones Cerebrales, Facultad de Ciencias Medicas, Universidad Nacional de Cuyo, Mendoza, Argentina.
Donoso
A O
AO
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