Prenatal cocaine exposure selectively reduces mesocortical dopamine release.
The effect of prenatal exposure to cocaine on the release of [3H]dopamine and on presynaptic dopamine autoreceptor regulation of [3H]dopamine release in prelabeled frontal cortical, cingulate cortical and striatal slices was investigated. The release of [3H]dopamine that is evoked by high K+ was reduced by 20 to 28% in the cortical regions but not in striatum. This effect was observed at 10 days of age and persisted up to postnatal day 120 in rabbits that were exposed to cocaine during gestational days 8 to 29. Spontaneous [3H]dopamine release was increased by 18 to 22% in frontal and cingulate cortices but not in striatum of the 10- but not the 50- or 120-day-old rabbit that was exposed to cocaine during gestational days 8 to 29. Total [3H]dopamine accumulated in brain slices examined on postnatal days 10, 50 or 120 was not affected by prenatal cocaine exposure. Incubation of slices with dopamine dose-dependently inhibited K(+)-evoked [3H]dopamine release in both cortical and striatal slices. Prenatal cocaine exposure enhanced the responsiveness to in vitro dopamine in the two cortical regions but not in striatum. Fetal cocaine exposure did not affect the levels of dopamine or its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, in frontal cortex or striatum. Similarly, no apparent differences in dopamine metabolism, as indicated by the ratio of 3,4-dihydroxyphenylacetic acid + homovanillic acid/dopamine, were observed in these brain areas. These findings demonstrate that prenatal cocaine exposure selectively affects depolarization-evoked [3H]dopamine release and its regulation by presynaptic dopamine autoreceptor in cortical areas.(ABSTRACT TRUNCATED AT 250 WORDS)
Wang
H Y
HY
Department of Pharmacology, Medical College of Pennsylvania, Philadelphia, USA.
Yeung
J M
JM
Friedman
E
E
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000633:toxicity*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011817:Rabbits
D003042:Cocaine; D004298:Dopamine