Prenatal cocaine exposure affects postnatal dopaminergic systems in various regions of the rat brain.
Pregnant female Sprague-Dawley rats were injected once daily with either 40 mg/kg cocaine hydrochloride or 0.9% saline from gestation day (GD)12 to GD 21. On postnatal day (PND)30, male offspring were sacrificed and fresh tissue from the striatum (ST) and nucleus accumbens (NA) was dissected for assessment of dopamine (DA) receptor affinity, DA uptake and DA release. 10(-6) M cocaine inhibited [3H]-DA uptake in ST tissue, whereas 10(-4) and 10(-5) M cocaine inhibited [3H]-DA uptake in the NA tissue of postnatally exposed cocaine offspring verses saline-treated controls (p < 0.05). DA release stimulated by 10(-6) M amphetamine was significantly reduced in both the ST (p < 0.001) and NA (p < 0.01) of postnatal offspring exposed to cocaine in utero compared with saline controls. In utero cocaine exposure did not influence offspring ST or NA dopamine 1 (D1) dissociation constant (Kd) or receptor density (Bmax). However, the treatment group experienced a significant increase of binding affinity for the ST D2 receptor with no change in D2 Bmax. The treatment group also experienced no change in D2 receptor binding affinity or number of binding sites in the NA. These results show that in utero exposure to cocaine results in altered postnatal dopaminergic function.
College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee 32307, USA.
S J
SJ
Choi
E
E
Mazzio
M G
MG
Kolta
K F
KF
Soliman
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009714:Nucleus Accumbens / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; D003042:Cocaine; D004298:Dopamine