Diazepam and progesterone produce sexually dimorphic actions on the rat EEG: role of the neonatal sexual differentiation process.
This study was designed to analyse if the effect of diazepam or progesterone on the wakeful rat EEG vary according to sex and neonatal sexual differentiation. Diazepam or progesterone was administered to males, females, neonatally castrated males and neonatally virilised females. Comparisons of drug actions were made versus baseline values. Both compounds produced clear sexual dimorphic responses, males being more sensitive than females. In normal males and neonatally virilised females diazepam produced a clear increase in the absolute power of fast frequencies. In normal females and neonatally castrated males this anxiolytic only produced a moderate increase in the absolute power of the beta 2 band. Regarding interparietal correlation, diazepam produced an increase in males in the alpha, beta 1 and beta 2 bands, while in females this drug caused a reduction in the same bands. Neonatally castrated males or virilised females showed an intermediate pattern. These data suggest that sexual dimorphism in diazepam action depends upon neonatal sexual differentiation. Progesterone, in contrast with diazepam, produced effects on the EEG that were also sexually dimorphic but independent of the sexual differentiation process. This steroid in males induced an increase in the absolute power of the fast bands of the EEG (alpha, beta 1 and beta 2) accompanied by an increased interparietal correlation of the alpha band. In females, progesterone only reduced the interparietal correlation in the fast theta and alpha bands. Data show similarities between diazepam and progesterone effects on the EEG that are discussed in the light of the anxiolytic-like and hypnotic properties of these compounds. A similar mechanism of action for both substances, involving the GABA(A) receptor, is sustained.
Fernández-Guasti
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Departamento de Farmacobiología, CINVESTAV, Calzada de los Tenorios 235, Col. Granjas Coapa, Mexico City, 14330 D.F., Mexico. jfernand@mail.cinvestav.mx
del Río Portilla
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IY
Ugalde
E
E
Corsi-Cabrera
M
M
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004569:Electroencephalography; D005260:Female; D008297:Male; D009919:Orchiectomy; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics; D013739:Testosterone / Q000008:administration & dosage
D014151:Anti-Anxiety Agents; D013739:Testosterone; D011374:Progesterone; D003975:Diazepam