Cocaine-induced alterations in the density of monoaminergic receptors in the embryonic guinea pig cerebral wall.
Quantitative receptor autoradiography was used to examine the effect of chronic cocaine exposure on the density of alpha1-, alpha2- and beta-adrenergic, 5-HT1A- and 5-HT2-serotonergic, and D1- and D2-dopaminergic receptors in the fetal guinea pig cerebral wall which contained forming motor area of the cerebral cortex. The pregnant guinea pig received two daily subcutaneous injections of 20 mg/kg cocaine beginning on the 20th day of pregnancy (E20). The control animals received injections of equivalent volume of saline. The receptor densities were examined between days 5-30 of the treatment, which corresponds to E25-E50. By the fifth day of treatment (E25), cocaine produced downregulation of all receptors studied throughout the entire depth of the fetal cerebral wall. More extended treatment, however, resulted in recovery of receptor levels. Finally, from days 20-30 of treatment (E40-E50) there was a significant upregulation of noradrenergic and dopaminergic receptor sites. These findings demonstrate that exposure to cocaine in utero can influence adrenergic, serotonergic, and dopaminergic receptors in the embryonic cerebral wall, which may lead to alteration in corticogenesis. Furthermore, the present study reveals that, in the course of chronic treatment, cocaine may completely reverse its receptor regulatory activity in the fetal brain.
Lidow
M S
MS
Department of Oral and Craniofacial Biological Sciences, University of Maryland, Baltimore 21201, USA. mlidow@umaryland.edu
Trakht
T
T
Howard
R L
RL
D018674:Adrenergic Antagonists / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D009044:Motor Cortex / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D011247:Pregnancy; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000378:metabolism; D013816:Thermodynamics; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
D018674:Adrenergic Antagonists; D018492:Dopamine Antagonists; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D018490:Serotonin Agents; D003042:Cocaine