Prenatal 3,4-methylenedioxymethamphetamine (ecstasy) exposure induces long-term alterations in the dopaminergic and serotonergic functions in the rat.
We investigated several aspects of the dopaminergic and serotonergic functions throughout brain development in rats prenatally exposed to MDMA ("ecstasy"). Pregnant rats were treated with MDMA (10 mg/kg s.c.) or saline from the 13th to the 20th day of gestation and studies were conducted on the progeny from both groups: (i) quantification of whole brain contents of DA, 5-HT and metabolites from the 14th day of embryonic life (E14) to weaning (21st day of postnatal life, P21); (ii) quantification of DA and 5-HT membrane transporters by autoradiography from E18 to adult age (P70); (iii) measurement of pharmacologically induced release of DA and 5-HT using microdialysis on adult (P70) freely moving rats; (iv) measurement of sucrose preference in adults (P70). Prenatally MDMA-exposed rats showed (i) a two-fold decrease of whole brain levels of 5-HT and 5-HIAA at P0; (ii) no effect on the DAT and SERT density; (iii) a strongly reduced pharmacologically induced release of DA and 5-HT at P70 in the striatum and hippocampus; and (iv) a significant 20% decrease in sucrose preference at P70. This study suggests that a prenatal exposure to MDMA induces transient and long-term neurochemical and behavioural modifications in dopaminergic and serotonergic functions.
Galineau
Laurent
L
INSERM U619, IFR135, Laboratoire de Biophysique Médicale and Pharmaceutique, Université François Rabelais des Sciences Pharmaceutiques, 31 avenue Monge, 37200 Tours, France.
Belzung
Catherine
C
Kodas
Ercem
E
Bodard
Sylvie
S
Guilloteau
Denis
D
Chalon
Sylvie
S
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000633:toxicity*; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography / Q000379:methods; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D004622:Embryo, Mammalian; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology; D006213:Hallucinogens / Q000633:toxicity*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D017551:Microdialysis / Q000379:methods; D009662:Nortropanes / Q000493:pharmacokinetics; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D012737:Sex Factors; D013997:Time Factors; D014439:Tyramine / Q000494:pharmacology
D015102:3,4-Dihydroxyphenylacetic Acid; D015104:3,4-Methylenedioxyamphetamine; D018759:Adrenergic Uptake Inhibitors; D004298:Dopamine; D005277:Fenfluramine; D006213:Hallucinogens; D006719:Homovanillic Acid; D006897:Hydroxyindoleacetic Acid; D026901:Membrane Transport Proteins; D009662:Nortropanes; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014439:Tyramine; C113010:N-(3-iodoprop-2-enyl)-2-beta-carbomethoxy-3-(4-methylphenyl)nortropane; C051800:3,4-methylenedioxyethamphetamine