Modulation of Puberty Terms and Sexual Behavior of Rats after Prenatal Exposure to Methyldopa, Phenibut, and Stress

Abstract

Prenatal effects of methyldopa, an inhibitor of noradrenaline synthesis (400 mg/kg/day), GABA agonist phenibut (100 mg/kg/day), or immobilization stress against the background of phenibut action on the timing of puberty and sexual behavior of male and female rats were investigated. The drugs were administered orally to pregnant animals during the last week of pregnancy (from the 15th to the 21st day). In experiments with prenatal stress, pregnant animals were immobilized daily for one hour during the same period of pregnancy. Some of them received phenibut 30 minutes prior to stressing. Application of phenibut to nonstressed pregnant animals led to accelerated maturation, and the use of methyldopa or phenibut resulted in disorders of sexual behavior of male and female offspring. However, phenibut weakened demasculinizing and feminizing effects of prenatal stress on male sexual behavior, as evidenced by the normalization of the latent periods of mountings and intromissions, their number, and a decrease in the number of lordosis reactions. Phenibut partially restored timing of puberty in those animals. The results obtained indicate the involvement of noradrenergic and GABA-ergic mechanisms in the prenatal programming of sexual behavior of animals, as well as the possibility of preventing its disorders in adult prenatally stressed rats by the activation of GABA-ergic receptors. Based on the results of these and previous studies, the concept of dualistic effects of hormonal and pharmacological neurotropic agents that are used during pregnancy has been proposed, according to which these agents may have either harmful or protective effect on the reproductive health and the ability of the offspring to respond to stressor factors.