Long-term consequences of prenatal exposure to cocaine or related drugs: effects on rat brain monoaminergic receptors.
Reports from both this laboratory and others indicate that prenatal exposure of rats to cocaine can produce alterations in development, activity and responses to environmental stimuli. In order to determine a biochemical basis for these effects, radioligand receptor-binding assays for different monoaminergic receptors were performed on rat brain tissues obtained from offspring of dams treated SC with saline, cocaine (15 mg/kg b.i.d.), amitriptyline (10 mg/kg) or amfonelic acid (AFA, 1.5 mg/kg). Male rat pups were fostered by surrogate dams and one rat per litter taken at 30, 60 or 180 days postnatal for determination of striatal and prefrontal cortical D2 receptors, prefrontal cortical 5HT2 receptors, cortical alpha 1-, alpha 2-, beta 1- and beta 2-adrenoceptors. Across all drug treatments and times, the only significant change was at 30 days of age when beta 1-adrenoceptors were increased 68% in the cocaine exposed pups--a time when these rats show hyperactivity--and at 180 days postnatal when a 20% decrease in DA2 receptor Bmax was observed. Also, cortical membrane Mg(2+)-dependent Na+, K(+)-ATPase activities and basal ATPase activities were unaltered by any of the treatments at any of the times. These results suggest that few changes have occurred in monoaminergic receptor sensitivity as a result of the exposure to these drugs during gestation. The behavioral changes that are known to occur following prenatal exposure to cocaine may be due to presynaptic alterations in neurotransmitter function rather than changes in postsynaptic receptors.
Henderson
M G
MG
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858.
McConnaughey
M M
MM
McMillen
B A
BA
D000375:Aging; D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D002540:Cerebral Cortex / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000502:physiology; D005260:Female; D008297:Male; D009268:Nalidixic Acid / Q000031:analogs & derivatives; D009287:Naphthyridines / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D009287:Naphthyridines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D011985:Receptors, Serotonin; D000639:Amitriptyline; D009268:Nalidixic Acid; D000254:Sodium-Potassium-Exchanging ATPase; D003042:Cocaine; C006486:amfonelic acid