Influences of gender, gonadectomy, and estrous cycle on GABA/BZ receptors and benzodiazepine responses in rats.
Benzodiazepines (BZ) and steroid hormone derivatives can potentiate the inhibitory actions of GABA through interactions with the GABAA/BZ/chloride ionophore complex. The present study examines whether the in vivo hormone milieu of rats modulates GABA/BZ receptors and/or benzodiazepine responses. The influences of gender, estrous cycle, and the diminution of steroid levels on GABA/BZ receptors and BZ anticonvulsant responses were tested by comparing these parameters in groups of intact male, intact female, orchidectomized, and ovariectomized rats. The hormonal milieu appears to modulate the GABA recognition site and possibly GABA-related responses in rats. This is evidenced by the decrease in cortical GABAA receptor affinity seen in females compared with other hormone groups and the gender-related difference observed in susceptibility to seizures induced by the GABA antagonist bicuculline. In cycling females, high circulating levels of progesterone were correlated with heightened seizure thresholds, suggesting that progestins serve a protective role in the control of seizure activity. Although a gender-related difference in cortical BZ binding affinity was observed, BZ receptor parameters in several other brain areas and BZ anticonvulsant responses were unaffected by physiological fluctuations in gonadal hormones.
Department of Pharmacology, University of South Carolina, School of Medicine, Columbia 29208.
M A
MA
Wilson
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000927:Anticonvulsants / Q000494:pharmacology; D001640:Bicuculline / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry / Q000502:physiology; D003975:Diazepam / Q000494:pharmacology; D004971:Estrus / Q000502:physiology*; D005260:Female; D005445:Flunitrazepam / Q000378:metabolism; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D011863:Radioimmunoassay; D011869:Radioligand Assay; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D012727:Sex Characteristics
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D011963:Receptors, GABA-A; D005445:Flunitrazepam; D003975:Diazepam; D001640:Bicuculline