Prenatal ethanol exposure alters sensitivity to the effects of apomorphine given alone and in combination with ethanol on locomotor activity in adult male mouse offspring.
Previous studies have indicated that prenatal ethanol (EtOH) exposure alters developing catecholamine (CA) systems and acute sensitivity to the locomotor stimulant effects of EtOH. The purpose of this study was to examine whether prenatal EtOH exposure influences the effects of the direct dopamine (DA) agonist apomorphine given alone as well as in combination with a low-dose stimulant challenge of EtOH. Standard lab chow or liquid diets containing either 25% EtOH-derived calories (EDC), or 0% EDC were given to pregnant C3H/He mice on gestation days 6-18. At 90 days of age, male offspring from each prenatal treatment group were monitored for 10 min in an open field following IP injections of apomorphine (0, 0.15, 0.3, 0.6, or 1.2 mg/kg) and either EtOH (1.5 g/kg) or saline. EtOH alone increased activity by 120-143% in all three groups of offspring. In control offspring, apomorphine dose-dependently decreased activity up to 74%-78% and blocked the stimulant effect of EtOH at all doses tested. However, in prenatal EtOH-exposed offspring, higher doses of apomorphine were significantly less effective in reducing both baseline and EtOH-stimulated activity compared to control mice. This effect is most likely not due to differences in pharmacokinetics, because blood EtOH concentrations were similar across apomorphine doses and prenatal treatment conditions. As such, these results support the hypothesis that prenatal exposure to EtOH alters acute sensitivity to the locomotor stimulant effects of EtOH, particularly under conditions in which CA systems mediating those effects are additionally challenged. In addition, the results suggest that prenatal EtOH exposure results in a long-lasting perturbation of central DA receptor sensitivity.
Becker
H C
HC
VA Medical Center, Research Service, Charleston, SC 29401.
Weathersby
R T
RT
Hale
R L
RL
D000818:Animals; D001058:Apomorphine / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D005260:Female; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009043:Motor Activity / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
D000431:Ethanol; D001058:Apomorphine