Effects of prenatal cocaine exposure upon postnatal development of neostriatal dopaminergic function.
Pregnant rats were injected twice daily with 20 mg/kg cocaine (or saline) from gestational day 10 to parturition. Brains from offspring were examined with quantitative receptor autoradiography [D1 receptor (D1R), D2 receptor (D2R) and dopamine transporter (DAT)] and quantitative in situ hybridization [D1R mRNA, D2R mRNA, preproenkephalin (PPE) mRNA] for markers of neostriatal dopaminergic function. Prenatal cocaine exposure did not alter postnatal development of striatal D1R sites, but D1R mRNA levels were reduced by a third at days 14 and 35. D2R sites were increased over control in lateral striatum by day 6, and remained elevated through postnatal day 35. Total D2R mRNA was increased over control in both medial and lateral striatum at 7 and 14 days but was equal to control at 35 days. Prenatal cocaine exposure increased DAT density at postnatal days 1 through 5, but reduced it at days 14 and 35; PPE mRNA expression was reduced at days 7, 14 and 35. Many of these results are similar to those found in experimental animals and humans following cocaine withdrawal.
Department of Psychiatric Medicine, University of Virginia School of Medicine, Charlottesville 22908.
C A
CA
Leslie
M W
MW
Robertson
A B
AB
Jung
J
J
Liebermann
J P
JP
Bennett
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism; D003042:Cocaine / Q000633:toxicity*; D004298:Dopamine / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D017403:In Situ Hybridization; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D017072:Neostriatum / Q000187:drug effects / Q000254:growth & development*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000096:biosynthesis; D013569:Synapses / Q000378:metabolism / Q000502:physiology
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011954:Receptors, Dopamine; C493216:Slc6a3 protein, rat; D003042:Cocaine; D004298:Dopamine