ENTRAINMENT OF THE FETAL HAMSTER CIRCADIAN PACEMAKER BY PRENATAL INJECTIONS OF THE DOPAMINE AGONIST SKF-38393

Prenatal treatment with the D-1-dopamine receptor agonist SKF 38393 or cocaine induces expression of the immediate-early gene c-fos in the f etal 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, th e 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 offsp ring from these treatment groups showed average phases that differed b y 11.3 hr, demonstrating that prenatal SKF 38393 set the phase of the offspring's circadian rhythms. These results suggest that the fetal ci rcadian 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 expressio n in the fetal hamster SCN and that mRNA for the D-1-dopamine receptor was present in the SCN at that time. It is possible that maternal ent rainment of the fetal circadian pacemaker, which normally occurs durin g development, is mediated by dopaminergic activation within the fetal hypothalamus.