Prenatal ethanol preferentially enhances reactivity of the dopamine D1 but not D2 or D3 receptors in offspring.

Reports of prenatal ethanol (ETOH) effects on the dopamine system are inconsistent. In an attempt to clarify this issue, dams were given 35% ethanol-derived calories as the sole nutrient source in a liquid diet from the 10th through the 20th day of gestation (ETOH). Controls were pair-fed (PF) an isocaloric liquid diet or given ad libitum access to laboratory chow (LC). Prenatal exposure to both liquid diets reduced body weight of offspring relative to LC controls, more so for ETOH than for PF exposure. Prenatal ETOH also decreased litter size and viability, relative to both LC and PF control groups. On postnatal days 21-23, male and female offspring were given an injection of saline vehicle or one of eight specific dopamine receptor agonists or antagonists. Immediately after injection subjects were placed in individual observation cages, and over the following 30 min, eight behaviors (square entries, grooming, rearing, circling, sniffing, yawning, head and oral movements) were observed and quantified. No prenatal treatment effects on drug-induced behaviors were observed for dopamine D2 (Apomorphine, DPAT or Quinpirole) or D3 (PD 152255, Nafadotride, Apo or Quin effects on yawning) receptor agonists or antagonists, or for the vehicle control. In contrast, prenatal treatment effects were seen with drugs affecting the dopamine D1 receptor. Both D1 agonists (SKF 38393) and antagonists (SCH 23390 and high doses of spiperone) altered behaviors, especially oral and sniffing behaviors, in a manner which suggested enhanced dopamine D1 drug sensitivity in both ETOH and PF offspring relative to LC controls. These results suggest that at this age, both sexes experience a prenatal undernutrition-linked increase in the behavioral response to dopamine D1 agonists and antagonists, which can be intensified by gestational exposure to alcohol.