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
Hc. Becker et al., 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, Neurotoxicology and teratology, 17(1), 1995, pp. 57-64
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 t
he 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 (CH)-H-3/He mice on gestation days
6-18. At 90 days of age, male offspring from each prenatal treatment g
roup were monitored for 10 min in an open field following IP injection
s 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 th
ree groups of offspring. In control offspring, apomorphine dose-depend
ently decreased activity up to 74%-78% and blocked the stimulant effec
t of EtOH at all doses tested. However, in prenatal EtOH-exposed offsp
ring, higher doses of apomorphine were significantly less effective in
reducing both baseline and EtOH-stimulated activity compared to contr
ol mice. This effect is most likely not due to differences in pharmaco
kinetics, because blood EtOH concentrations were similar across apomor
phine doses and prenatal treatment conditions. As such, these results
support the hypothesis that prenatal exposure to EtOH alters acute sen
sitivity to the locomotor stimulant effects of EtOH, particularly unde
r conditions in which CA systems mediating those effects are additiona
lly challenged. In addition, the results suggest that prenatal EtOH ex
posure results in a long-lasting perturbation of central DA receptor s
ensitivity.