Effects of prenatal cocaine exposure on the nigrostriatal dopamine system: an in vivo microdialysis study in the rat.
Pregnant rats were given injections of saline (0.5 ml/kg) or cocaine (10 mg/kg, 20 mg/ml, s.c.) twice daily between gestational days 7-21. Offspring were examined by microdialysis between postnatal days 10-125 to study the effects of prenatal cocaine exposure on the nigrostriatal dopamine (DA) system. Twenty-min dialysis samples were collected and assayed for DA, DOPAC and HVA. After four baseline samples, the rat was exposed to 20 min of intermittent tail pinch and monitored for four samples; then each rat received an acute injection of cocaine (20 mg/kg, i.p.) and six additional samples were collected. Basal dialysate concentrations of all DA markers, estimated from pre-implantation calibration of the probes, were markedly reduced in young rats ('pups', 10-30 days old) as compared with adult rats (40-125 days old). Compared to control pups, basal DA, as well as DOPAC and HVA, were elevated in the prenatal-cocaine pups. Tail pinch (a mild stressor) produced a significant increase in DA only in the pups prenatally exposed to cocaine. The increase in basal DA induced by an acute cocaine injection (20 mg/kg) was also greater and more prolonged in the prenatal-cocaine pups. In older rats (40-125 days) there were no group differences in any of the DA parameters. Thus prenatal exposure to cocaine produces an activation of the DA system which persists after birth but returns to normal in older rats.
Keller
R W
RW
Department of Pharmacology and Toxicology, Albany Medical College, NY 12208.
Maisonneuve
I M
IM
Nuccio
D M
DM
Carlson
J N
JN
Glick
S D
SD
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism; D003042:Cocaine / Q000378:metabolism / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D007267:Injections; D017551:Microdialysis; D009994:Osmolar Concentration; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D013312:Stress, Physiological / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism*
D003042:Cocaine; D004298:Dopamine