Characterization of the dopamine receptor system in adult rhesus monkeys exposed to cocaine throughout gestation.
BACKGROUND
Cocaine use during pregnancy is associated with alterations in the dopamine (DA) system in the fetal brain. However, little is known about the effects of prenatal cocaine exposure on the postnatal dopaminergic system.


OBJECTIVE
The objective of the study was to examine DA receptor function in adult monkeys that were prenatally exposed to cocaine.


METHODS
Male and female rhesus monkeys (approximately 13 years old) that had been prenatally exposed to cocaine (n = 10) and controls (n = 10) were used in all studies. First, DA D2-like receptor availability was assessed using positron emission tomography and the D2-like receptor radiotracer [(18)F]fluoroclebopride (FCP). Next, D(3) receptor function was assessed by measuring quinpirole-induced yawning (0.03-0.3 mg/kg). Finally, D1-like receptor function was examined by measuring eye blinking elicited by the high-efficacy D1-like receptor agonist SKF81297 (0.3-3.0 mg/kg).


RESULTS
There were no differences between groups or sexes in D2-like receptor availability in the caudate nucleus, putamen or amygdala. However, quinpirole elicited significantly more yawns in prenatally cocaine-exposed monkeys compared with control monkeys. A significant correlation between gestational dose of cocaine and peak effects of quinpirole was observed. In all monkeys, administration of SKF81297 elicited dose-dependent increases in eye blinks that did not differ between groups.


CONCLUSIONS
These findings suggest that prenatal cocaine exposure can have long-term effects on DA D(3) receptor function in adults.
Hamilton
Lindsey R
LR
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, 546 NRC, Medical Center Blvd., Winston-Salem, NC 27157-1083, USA.
Czoty
Paul W
PW
Gage
H Donald
HD
Nader
Michael A
MA
D000818:Animals; D001549:Benzamides / Q000032:analysis; D001552:Benzazepines / Q000494:pharmacology; D001767:Blinking / Q000187:drug effects; D003042:Cocaine / Q000633:toxicity*; D018491:Dopamine Agonists / Q000494:pharmacology; D005260:Female; D005462:Fluorine Radioisotopes / Q000032:analysis; D008253:Macaca mulatta; D008297:Male; D010880:Piperidines / Q000032:analysis; D011247:Pregnancy; D011270:Pregnancy, Animal; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D019257:Quinpirole / Q000494:pharmacology; D011869:Radioligand Assay / Q000379:methods; D017447:Receptors, Dopamine D1 / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000187:drug effects*; D015000:Yawning / Q000187:drug effects
D001549:Benzamides; D001552:Benzazepines; D018491:Dopamine Agonists; D005462:Fluorine Radioisotopes; D010880:Piperidines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C083673:fluoroclebopride; D019257:Quinpirole; C067113:SK&F 81297; D003042:Cocaine
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