Moderate-level prenatal alcohol exposure alters striatal dopamine system function in rhesus monkeys.
BACKGROUND
Moderate prenatal alcohol exposure can cause impairments even in the absence of gross morphological defects associated with fetal alcohol syndrome. The basal ganglia, which include the dopamine-rich striatum, are sensitive to fetal alcohol-induced injury. In this study, we manipulated the timing of moderate-level alcohol exposure and compared the risk of adverse effects on striatal dopamine (DA) system function in rhesus monkeys.


METHODS
Thirty-five young adult rhesus monkeys (Macaca mulatta) from four groups of females were assessed: (1) an early alcohol-exposed group (n=9), in which mothers voluntarily consumed 0.6 g/kg alcohol solution on gestational days 0 through 50; (2) a middle-to-late gestation alcohol-exposed group (n=7), in which mothers voluntarily consumed 0.6 g/kg alcohol solution on gestational days 50 through 135; (3) a continuous-exposure group (n=9), in which mothers voluntarily consumed 0.6 g/kg alcohol solution on days 0 through 135; and (4) controls (n=10), in which mothers voluntarily consumed an isocaloric control solution on gestational days 0 through 50, 50 through 135, or 0 through 135. We studied striatal DA system function by positron emission tomography in separate scans for trapping of [(18)F]fallypride and 6-[(18)F]fluoro-m-tyrosine to assess striatal DA D2 receptor (D2R) binding and DA synthesis, respectively, via dopadecarboxylase activity.


RESULTS
Moderate-level alcohol exposure during early gestation and continuous exposure throughout gestation (early + middle-to-late exposure) reduced the striatal D2R binding to DA synthesis ratio, whereas middle-to-late alcohol gestation exposure increased the striatal D2R binding to DA synthesis ratio. The continuous-exposure group showed the largest effect. Moreover, the D2R binding/DA synthesis ratio was related to neonatal neurobehavior measures in control monkeys, but these relationships were disrupted in the fetal alcohol-exposed monkeys.


CONCLUSIONS
These results suggest that the vulnerability of the DA system to the effects of moderate doses of alcohol during gestation depend on the timing of the alcohol exposure. Early-gestation moderate alcohol exposure resulted in a reduction or blunting of dopaminergic function in adulthood, whereas middle to late exposure (without early exposure) either induced the opposite pattern or heightened dopaminergic function. Continuously exposed monkeys showed the largest effect, suggesting that the sooner women stop drinking, the better it is for the fetus.
Schneider
Mary L
ML
Department of Kinesiology, the Harlow Center for Biological Psychology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA. schneider@education.wisc.edu
Moore
Colleen F
CF
Barnhart
Todd E
TE
Larson
Julie A
JA
DeJesus
Onofre T
OT
Mukherjee
Jogeshwar
J
Nickles
Robert J
RJ
Converse
Alexander K
AK
Roberts
Andrew D
AD
Kraemer
Gary W
GW
D000818:Animals; D001549:Benzamides; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D008253:Macaca mulatta; D008297:Male; D049268:Positron-Emission Tomography; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2 / Q000032:analysis / Q000187:drug effects*
D001549:Benzamides; C094948:N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D000431:Ethanol