LONG-TERM EFFECTS OF EARLY COCAINE EXPOSURE ON THE LIGHT RESPONSIVENESS OF THE ADULT CIRCADIAN TIMING SYSTEM

Early cocaine exposure is associated with a wide variety of neurobehav ioral and teratogenic effects. The current study was conducted to dete rmine the long-term effects of such exposure on the hamster circadian timing system. The circadian system drives rhythms in a tremendous div ersity of physiological, behavioral, and endocrine functions. The feta l circadian pacemaker has recently been shown to express a functional D-1 dopamine system that is involved in maternal-fetal entrainment. Ma ternally administered cocaine: acting on the fetal clock. could theref ore potentially have long-lasting effects on exposed offspring. Pregna nt SCN-lesioned hamsters or their pups, maintained in constant dim ill umination (DD), were;administered cocaine (30 mg/kg, SC, N = 10 litter s) or saline vehicle (N = 5 litters) from embryonic (E) day 15 [day of mating = E0] through postnatal (P) day 5. Upon weaning (P21), cocaine - and saline-treated offspring were placed in individual running wheel s for a period of 5-6 weeks. Individuals were then challenged with 1-h light pulses at three circadian times (CT7, CT14, CT18). Cocaine-trea ted litters had a statistically significant mean phase advance of +0.3 2 h at CT14 compared with the mean phase delay of -2.13 h of the salin e-treated litters. No significant differences were seen at the other t wo circadian times, although there was heterogeneity in the responses among cocaine-treated animals. This represents the first demonstration of an effect of perinatal cocaine on the circadian timing system. Tog ether with the recent demonstration of D-1 receptors in the human SCN, these findings raise the possibility that gestational cocaine abuse b y humans may also lead to later disturbances in the circadian timing s ystem. (C) 1998 Elsevier Science Inc.