Effects of prenatal cocaine exposure on amphetamine-induced dopamine release in the caudate nucleus of the adult rabbit.
Acute amphetamine (AMPH) challenge has been used to probe the neurochemical and behavioral integrity of dopaminergic neurons under various conditions including prenatal cocaine exposure. In this study, we employed in vivo microdialysis to examine the effects of prenatal cocaine exposure on AMPH-induced dopamine (DA) release in the caudate nucleus of the awake adult rabbit. Pregnant rabbits were given intravenous injections of either saline or cocaine (4 mg/kg) twice a day from gestational day 8 (G8) through G29. Microdialysis was performed in adult saline and cocaine progeny at approximately postnatal day 70 (P70). There were no significant differences between cocaine and saline progeny in their basal concentrations of DA or its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). AMPH (5 mg/kg, i.v.) significantly increased extracellular DA in the caudate of both groups. However, AMPH-induced DA release was 2 to 3-fold greater in cocaine progeny than in the saline controls. Although, DOPAC decreased in both groups following AMPH injection, there was no significant group effect. In addition, there were no significant changes in concentrations of HVA. AMPH is known to release DA by a mechanism of exchange diffusion via the presynaptic DA transporter (DAT). Therefore, we examined the binding of [(3)H]WIN 35,428 to membrane fractions prepared from fresh caudate tissue to determine whether prenatal exposure to cocaine had altered the density (B(max)) or affinity (K(d)) of the DAT. While the B(max) for [(3)H]WIN 35,428 binding increased 3-fold between P3 and P120, there were no significant differences between saline and cocaine progeny at any age examined. The K(d) for [(3)H]WIN 35,428 binding did not change with postnatal age and did not differ between cocaine and saline progeny. These findings suggest that prenatal exposure to cocaine produces a long-term increase in the size of the presynaptic, AMPH releasable, cytoplasmic pool of DA.
Department of Pharmacology, MCP Hahnemann University, Philadelphia, PA 19129, USA. du@mcphu.edu
W
W
Du
V J
VJ
Aloyo
P S
PS
Pazdelski
J A
JA
Harvey
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D017551:Microdialysis; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017729:Presynaptic Terminals / Q000187:drug effects; D011817:Rabbits; D011869:Radioligand Assay
D018765:Dopamine Uptake Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D000661:Amphetamine; D003042:Cocaine; D004298:Dopamine; D006719:Homovanillic Acid