The Circadian System Is a Target and Modulator of Prenatal Cocaine Effects

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dc.contributor.author Shang, Eva H. en_US
dc.contributor.author Zhdanova, Irina V. en_US
dc.date.accessioned 2012-01-11T23:13:28Z
dc.date.available 2012-01-11T23:13:28Z
dc.date.issued 2007-7-11 en_US
dc.identifier.citation Shang, Eva H., Irina V. Zhdanova. "The Circadian System Is a Target and Modulator of Prenatal Cocaine Effects" PLoS ONE2(7): e587. (2007) en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://hdl.handle.net/2144/3325
dc.description.abstract BACKGROUND. Prenatal exposure to cocaine can be deleterious to embryonic brain development, but the results in humans remain controversial, the mechanisms involved are not well understood and effective therapies are yet to be designed. We hypothesize that some of the prenatal effects of cocaine might be related to dysregulation of physiological rhythms due to alterations in the integrating circadian clock function. METHODOLOGY AND PRINCIPLE FINDINGS. Here we introduce a new high-throughput genetically well-characterized diurnal vertebrate model for studying the mechanisms of prenatal cocaine effects by demonstrating reduced viability and alterations in the pattern of neuronal development following repeated cocaine exposure in zebrafish embryos. This effect is associated with acute cocaine-induced changes in the expression of genes affecting growth (growth hormone, zGH) and neurotransmission (dopamine transporter, zDAT). Analysis of circadian gene expression, using quantitative real-time RT-PCR (QPCR), demonstrates that cocaine acutely and dose-dependently changes the expression of the circadian genes (zPer-3, zBmal-1) and genes encoding melatonin receptors (zMelR) that mediate the circadian message to the entire organism. Moreover, the effects of prenatal cocaine depend on the time of treatment, being more robust during the day, independent of whether the embryos are raised under the light-dark cycle or in constant light. The latter suggests involvement of the inherited circadian factors. The principal circadian hormone, melatonin, counteracts the effects of cocaine on neuronal development and gene expression, acting via specific melatonin receptors. CONCLUSIONS/SIGNIFICANCE. These findings demonstrate that, in a diurnal vertebrate, prenatal cocaine can acutely dysregulate the expression of circadian genes and those affecting melatonin signaling, growth and neurotransmission, while repeated cocaine exposure can alter neuronal development. Daily variation in these effects of cocaine and their attenuation by melatonin suggest a potential prophylactic or therapeutic role for circadian factors in prenatal cocaine exposure. en_US
dc.description.sponsorship National Institutes of Health (DA1541801, MH 065528); National Institute on Drug Abuse (DA-4-7733) en_US
dc.language.iso en en_US
dc.publisher Public Library of Science en_US
dc.title The Circadian System Is a Target and Modulator of Prenatal Cocaine Effects en_US
dc.type article en_US
dc.identifier.doi 10.1371/journal.pone.0000587 en_US
dc.identifier.pubmedid 17622340 en_US
dc.identifier.pmcid 1899232 en_US

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