Cocaine binding sites in fetal rat brain: implications for prenatal cocaine action.
Binding of [3H]cocaine to membrane preparations from whole fetal rat brain was studied. High-affinity binding (10 nM cocaine) was detected as early as gestational day (GD) 15 and steadily increased across subsequent development. Saturation studies comparing [3H]cocaine binding at GD20 and adulthood yielded similar KD values, and LIGAND analyses favored a two-site model if an extended range of [3H]cocaine concentrations was used. Various monoamine uptake inhibitors displaced labeled cocaine with potencies consistent with the idea that [3H]cocaine labels the dopamine (DA), serotonin (5-HT), and possibly also the norepinephrine (NE) transporters in whole fetal brain preparations. Synaptosomal DA uptake was well developed by GD20, as was the potency of cocaine to inhibit such uptake. The results indicate that functional, monoamine transporter related cocaine binding sites are present in the fetal rat brain. Such sites are likely to play an important role in mediating the direct interactions of prenatally-administered cocaine with developing monoaminergic systems in both animals and humans.
Meyer
J S
JS
Department of Psychology, University of Massachusetts, Amherst 01003.
Shearman
L P
LP
Collins
L M
LM
Maguire
R L
RL
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D003042:Cocaine / Q000378:metabolism* / Q000493:pharmacokinetics; D004298:Dopamine / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D014179:Neurotransmitter Uptake Inhibitors; D011955:Receptors, Drug; D012701:Serotonin; D003042:Cocaine; D004298:Dopamine; D009638:Norepinephrine