Prenatal treatment with the D1-dopamine receptor agonist SKF 38393 or cocaine induces expression of the immediate-early gene c-fos in the fetal rat suprachiasmatic nucleus (SCN) (Weaver et al., 1992). Because the induction of c-fos gene expression in the SCN has been implicated in the entrainment of circadian rhythms by light in mature animals, the present study investigated whether prenatal dopaminergic activation entrains the fetal circadian pacemaker. Injections of SKF 38393 (8 mg/kg) were given to pregnant, SCN-lesioned hamsters during the last 5 d of gestation and the phases of the offspring's wheel-running activity rhythms were measured on postnatal day 20. Pregnant hamsters were each given two injections/day 12 hr apart, but only one of the injections each day contained SKF 38393. One group of hamsters received the drug at 0800 hr while another group received the drug at 2000 hr. The offspring from these treatment groups showed average phases that differed by 11.3 hr, demonstrating that prenatal SKF 38393 set the phase of the offspring's circadian rhythms. These results suggest that the fetal circadian pacemaker can be entrained by dopaminergic activation. In situ hybridization using cRNA probes demonstrated that a single injection of SKF 38393 on the last day of gestation induced c-fos gene expression in the fetal hamster SCN and that mRNA for the D1-dopamine receptor was present in the SCN at that time. It is possible that maternal entrainment of the fetal circadian pacemaker, which normally occurs during development, is mediated by dopaminergic activation within the fetal hypothalamus.

Sexually dimorphic regions are described in two areas of the guinea pig brain: the medial preoptic area (MPOA) and the bed nucleus of the stria terminalis (BNST). The volume of a darkly staining portion of the MPOA is approximately d-fold larger in male than in female guinea pigs, and the volume of a darkly staining portion of the BNST is approximately 36% larger in male than in female animals. The sex differences in both of these areas are present in animals that have been gonadectomized as adults as well as in intact animals, suggesting that they result from differences between the sexes in the hormonal environment during early development. Both the MPOA and the BNST bind high levels of gonadal steroids early in life, during the period when functional differentiation occurs. It is possible that dramatic morphological sex differences characterize such steroid-binding areas. Furthermore, these sexually dimorphic areas may form an anatomically and functionally interrelated system. Attention to these possibilities may help elucidate more precisely the neural basis for sexually dimorphic functions, as well as the basic mechanisms underlying sexual differentiation of behavior and the brain.Gonadal hormones have powerful influences on sexual differentiation of the brain in mammals. For example, a genetic female rat that is treated with testosterone during the perinatal period of development will be masculinized with respect to a variety of neural functions, including gonadotropin regulation, reproductive behavior, food intake, aggression, and performance on certain types of learning tasks. Although these influences have been studied most extensively in the rat, similar effects have been documented in mice, hamsters, gerbils, guinea pigs, dogs, cattle, ferrets, sheep, marmoset and rhesus monkeys, and even, to some extent, in human beings (for reviews see Gorski, 1979; Goy and McEwen, 1980; Hines, 1982).A recent development in this field has been the identification of sex differences in the structure of the brain that may underlie these functional changes.