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 neurobehavioral and teratogenic effects. The current study was conducted to determine the long-term effects of such exposure on the hamster circadian timing system. The circadian system drives rhythms in a tremendous diversity of physiological, behavioral, and endocrine functions. The fetal circadian pacemaker has recently been shown to express a functional D1 dopamine system that is involved in maternal-fetal entrainment. Maternally administered cocaine, acting on the fetal clock, could therefore potentially have long-lasting effects on exposed offspring. Pregnant SCN-lesioned hamsters or their pups, maintained in constant dim illumination (DD), were administered cocaine (30 mg/kg, SC, N = 10 litters) 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 wheels for a period of 5-6 weeks. Individuals were then challenged with 1-h light pulses at three circadian times (CT7, CT14, CT18). Cocaine-treated litters had a statistically significant mean phase advance of +0.32 h at CT14 compared with the mean phase delay of 2.13 h of the saline-treated litters. No significant differences were seen at the other two 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. Together with the recent demonstration of D1 receptors in the human SCN, these findings raise the possibility that gestational cocaine abuse by humans may also lead to later disturbances in the circadian timing system.
Strother
W N
WN
Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, OH, USA. wstrothe@iupui.edu
Vorhees
C V
CV
Lehman
M N
MN
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects*; D003042:Cocaine / Q000493:pharmacokinetics / Q000633:toxicity*; D006224:Cricetinae; D018765:Dopamine Uptake Inhibitors / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D008027:Light; D008647:Mesocricetus; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
D018765:Dopamine Uptake Inhibitors; D003042:Cocaine