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.

Amplitude reduction in visual event-related potentials as a function of sleep deprivation.

Eight adult males were subjected to 40 hours of total sleep deprivation (TSD). Reaction time in a visual task and electroncephalographam (C3) were evaluated every 2 hours. One second of EEG before the stimuli was Fourier-transformed, and 750 ms after target and nontarget stimuli were averaged and visual event-related potentials (ERP) were obtained. Factorial analysis identified time windows that showed significant amplitude reduction and longer latencies with TSD: (1) 140 to 288 ms (P180-N242-P281); (2) 288 to 413 ms and 601 to 749 ms (N382; P718) and; (3) 531 to 601 ms (N500). Effect was strongest for N382 and P718, the amplitudes of which dropped to 20% of original size. The entire waveform recovered initial amplitudes and latencies after recovery sleep except for P718 latency. Waveforms within similar time intervals have been associated with attentional gating, sensory discrimination, target selection, uncertainty and decision processes. Amplitudes of the visual ERP were inversely correlated with hours of TSD, reaction time, and absolute power of the prestimulus EEG. Present results clearly show changes in fundamental neurophysiologic mechanisms as a result of TSD, indicating variability and reduction of the alertness mechanisms and changes in thalamocortical gating affecting attention, discrimination and decision-making.

Effect of diazepam and sex hormones on EEG of gonadectomized male and female rats.

Waking EEG was recorded from left and right parietals in 60 adult Wistar rats gonadectomized after puberty during 5 days, 1 as baseline, 1 with vehicle and 1 with 10 mg/kg i.m. of diazepam with hormonal treatment (either testosterone propionate, 5-alpha-dihydrotestosterone or vehicle in males and progesterone, estradiol benzoate or vehicle in females). Quantitative EEG analysis showed that: diazepam in gonadectomized males increased absolute power of alpha, beta 1 and beta 2, increased interparietal correlation of delta and decreased interparietal correlation of slow theta, fast theta and beta 1, whereas in gonadectomized females, diazepam additionally decreased slow and fast theta absolute power. EEG effects were not modified by testosterone propionate or 5-alpha-dihydrotestosterone treatment in males. Diazepam plus estradiol rendered the female EEG response similar to the gonadectomized or testosterone-treated males response; diazepam plus progesterone induced the same response in females as in gonadectomized females and additionally induced interparietal asymmetry and decreased interparietal correlation of all EEG bands. Present results and information on the effects of diazepam on interparietal coupling of EEG and demonstrate that the EEG response to diazepam in adult rats is sexually dimorphic and depends on sex as well as on activational effects of gonadal steroids.

Effects of prenatal testosterone on sex and age differences in behavior elicited by stimulus pups in the rat.

From Days 14 to 19, pregnant Wistar rats were treated with either 2 mg of testosterone propionate (TP) or vehicle. Thirty-, 60-, and 90-day-old offspring were tested individually during 15 min daily on 4 days with a stimulus litter, and pup-oriented and non-pup-oriented behaviors were recorded. Sex differences in pup-oriented behaviors observed in oil groups were eliminated by TP treatment, which affected mainly females. Additionally, TP treatment increased the frequency of self-grooming and decreased the time spent near the pups and the frequency of sniffing and pawing only at 90-days of age. Hiding behavior only occurred at 30 days of age, while pawing near the pups and lying-down behavior was observed mainly in adults. Results show that sex differences in behavior are present before subjects become sensitized to show evident maternal behavior, and suggest that prenatal androgens play an important role in the manifestation of these sex differences and that its effects depend on developmental factors.

Sex differences in EEG in adult gonadectomized rats before and after hormonal treatment.

EEG activity was recorded from the left and right parietal cortex in adult male and female Wistar rats that were gonadectomized (GNX) after puberty during 2 days without and 3 days with hormonal treatment (either testosterone propionate, 5 alpha-DHT or vehicle in males and progesterone, estradiol benzoate or vehicle in females). In contrast to EEG characteristics reported for intact rats, GNX abolished right over left parietal activation in both sexes and, sex differences in EEG interhemispheric correlation and in theta and delta relative power in the right parietal; additionally GNX males showed higher absolute power than females. Hormonal treatment reestablished interparietal asymmetry in both sexes and a lack of sex differences in absolute power, however, it was not enough to reestablish sex differences in delta and theta proportion in the right parietal nor in interhemispheric correlation. Differential effects were obtained with testosterone propionate and 5 alpha-DHT in males suggesting that activational effects of testosterone on EEG are probably exerted through testosterone or its aromatized metabolites. The results of our study indicate that the activational effects of gonadal steroids after puberty are necessary for maintaining sex differences in the EEG of the adult rat.

Effects of prenatal testosterone treatment on sex differences in the EEG activity of the rat.

Pregnant rats were injected either with 2 mg of testosterone propionate or with vehicle on days 14 to 19 of gestation. Ano-genital distance (AGD) and body weight (b.wt.) of the offspring were measured at 10, 20, 30, 45, 60, 75 and 90 days of age. Between 98 and 104 days of age the EEG activity was monopollarly recorded with electrodes implanted in the left and right parietal cortex. Males showed higher interhemispheric correlation than females in delta, theta, alpha] and the total band. Delta relative power (RP) was lower and theta RP was higher in males than in females. These sex differences were eliminated with the prenatal testosterone treatment (PTT), which exerted a masculinizing effect on females. Absolute power (AP) did not show sex differences, but PTT produced an increase in the AP of all bands, except for beta2, regardless of sex. PTT increased the AGD at all ages, except 90 days. This increase was significant only in females at 10, 30, 45, 60 and 75 days of age. PTT increased the b.wt. at all ages, regardless of sex. These data indicate that the organizational action of sex hormones during the prenatal period plays an important role in the establishment of EEG sex differences in the rat.