Monoamine transporters and the neurobehavioral teratology of cocaine.
Prenatal cocaine exposure has been associated with various postnatal behavioral abnormalities in human infants, and also with changes in locomotor activity, learning deficits, and altered responses to drug challenge in nonhuman offspring. Several studies have further demonstrated that cocaine exerts an activating effect on fetal behavior. A variety of mechanisms have been proposed to account for the neurobehavioral teratogenic effects of developmental cocaine treatment, including inhibition of fetal brain neurotransmitter uptake and fetal hypoxemia secondary to constriction of the uteroplacental vascular bed. In support of the hypothesis that cocaine effects may be mediated partly by monoamine uptake inhibition, we and other investigators have recently demonstrated the presence of functional dopamine (DA), serotonin (5-HT), and norepinephrine (NE) transporters in the fetal rat brain. Transporter-related cocaine recognition sites are found in a number of fetal brain areas and could mediate the acute effects of cocaine on these areas as well as developmental changes that are manifested postnatally. For example, DA transporter blockade may underlie the above-mentioned activational effects of cocaine on fetal behavior. Time-dependent changes in DA or 5-HT transporter expression produced by prenatal cocaine exposure could likewise play an important role in some of the behavioral effects observed when offspring are tested postnatally.
Meyer
J S
JS
Department of Psychology, University of Massachusetts, Amherst 01003, USA.
Shearman
L P
LP
Collins
L M
LM
D000818:Animals; D001519:Behavior / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D015306:Biogenic Monoamines / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology; D003042:Cocaine / Q000633:toxicity*; D005260:Female; D006801:Humans; D009294:Narcotics / Q000633:toxicity*; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D013723:Teratogens / Q000633:toxicity*
D015306:Biogenic Monoamines; D002352:Carrier Proteins; D009294:Narcotics; D013723:Teratogens; D003042:Cocaine