Reduced serotonin release and serotonin uptake sites in the rat nucleus accumbens and striatum after prenatal cocaine exposure.
This study was designed to assess the effects of prenatal cocaine exposure on the development of the serotonergic system. Pregnant Sprague-Dawley rats received daily sc injections of either cocaine (30 mg/kg) or saline from gestation day 7 (GD 7) to GD 20. At 1 week postnatal, all pups were killed and tissues containing the striatum and nucleus accumbens dissected out. In superfusion experiments, tissue slices were incubated with [3H]serotonin ([3H]5-HT) for 30 min and then superfused. The [3H]5-HT release was induced by exposures to the following treatments: electrical stimulations (20 mA or 40 mA, 0.5 Hz, 4 min), the medium containing 15 or 30 mM potassium (2 min), fenfluramine (1 or 2 microM for 2 min), para-chloroamphetamine (1 or 2 microM for 2 min), methiothepin (1 or 2 microM for 2 min), and fluoxetine (1 or 2 microM for 2 min). The results showed that the treatment-induced [3H]5-HT releases were all significantly less pronounced in the pups prenatally exposed to cocaine than in those prenatally exposed to saline regardless of the mechanisms by which the treatment increases extracellular 5-HT. Saturation analysis showed that the Bmax of [3H]citalopram binding sites was also significantly lower in the pups prenatally treated with cocaine than in those prenatally treated with saline. The results are consistent with the concept that less serotonergic innervation may exist in the examined brain areas of cocaine-treated offspring at 1 week postnatal, and support the hypothesis that prenatal cocaine exposure affects the postnatal development of the serotonergic system.
Yan
Qing Shan
QS
Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine, Peoria, IL 61656, USA. qsy@uic.edu
D000818:Animals; D000831:Animals, Newborn; D015283:Citalopram; D003042:Cocaine / Q000633:toxicity*; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000503:physiopathology; D004558:Electric Stimulation; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005473:Fluoxetine / Q000494:pharmacology; D008719:Methiothepin / Q000494:pharmacology; D017072:Neostriatum / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D018490:Serotonin Agents / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors; D010133:p-Chloroamphetamine / Q000494:pharmacology
D015283:Citalopram; D003042:Cocaine; D005277:Fenfluramine; D005473:Fluoxetine; D008719:Methiothepin; D011188:Potassium; D012701:Serotonin; D018490:Serotonin Agents; D017367:Selective Serotonin Reuptake Inhibitors; D010133:p-Chloroamphetamine