Prenatal cocaine exposure disrupts the development of the serotonergic system.
Prenatal cocaine exposure has been found to result in a number of neurobehavioral abnormalities in both clinical and laboratory studies. We have previously shown that cocaine inhibits the growth of developing serotonin neurons in culture. This study examines the effects of cocaine on the developing serotonin system in vivo. Pregnant rats were injected with cocaine (40 mg/kg s.c.) from gestational day 13 to parturition. One group of rats was additionally injected on postnatal days 1-5 with cocaine (10 mg/kg s.c.). [3H]Paroxetine, a selective ligand for the serotonin uptake carrier, was used to quantify serotonin terminal fiber density at one day, one week, and four weeks postnatal. Cocaine exposure was found to significantly decrease [3H]paroxetine-labelled sites and thus the density of serotonin fibers in the cortex and hippocampus at one day and one week postnatal. By four weeks postnatal, no significant effect was observed, indicating that a recovery had occurred. Serotonin immunocytochemistry performed at one month revealed normal fiber distribution in the cortex but a loss of fibers in the CA1 and CA2 hippocampal fields. Postnatal treatment alleviated the effects of prenatal cocaine exposure, resulting in [3H]paroxetine binding levels at one week which were comparable to and, in the cortex, even higher than those of saline controls. We conclude that cocaine delays the maturation of the serotonin system when administered prenatally but may accelerate maturation when administered both pre- and postnatally.
Akbari
H M
HM
Department of Biology, New York University, NY 10003.
Kramer
H K
HK
Whitaker-Azmitia
P M
PM
Spear
L P
LP
Azmitia
E C
EC
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D003042:Cocaine / Q000633:toxicity*; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D007150:Immunohistochemistry; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D009412:Nerve Fibers / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D017374:Paroxetine; D010880:Piperidines / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000378:metabolism
D010880:Piperidines; D012702:Serotonin Antagonists; D012701:Serotonin; D017374:Paroxetine; D003042:Cocaine