REDUCED SENSITIVITY TO THE EFFECTS OF CLONIDINE ON ETHANOL-STIMULATEDLOCOMOTOR-ACTIVITY IN ADULT-MOUSE OFFSPRING PRENATALLY EXPOSED TO ETHANOL

Prenatal exposure to ethanol (EtOH) alters developing catecholamine (C A) systems and acute sensitivity to the locomotor stimulant effects of EtOH. As an extension of previous work involving CA agents, this stud y addressed whether prenatal EtOH exposure influences central norepine phrine (NE) systems by examining the motoric effects of the direct alp ha(2) adrenoreceptor agonist clonidine given alone and in combination with a low-dose stimulant challenge of EtOH. Standard lab chow or liqu id diets containing either 25% EtOH-derived calories (EDC), or 0% EDC (pair-fed group) were given to pregnant C3H/He mice on gestation days 6-18. At 90 days of age, male offspring from each prenatal treatment g roup were monitored for 10 minutes in an open field following IP injec tions of clonidine (0, 0.0125, 0.025, or 0.05 mg/kg) and either EtOH ( 1.5 g/kg) or saline. In control offspring, clonidine suppressed locomo tor activity and attenuated the stimulant response to EtOH in a dose-d ependent fashion. In contrast, clonidine given alone did not suppress, but appeared to stimulate, activity in prenatal EtOH-exposed offsprin g. Furthermore, the ability of clonidine to attenuate the locomotor st imulant properties of EtOH was greatly reduced in prenatal EtOH-expose d animals. Taken together, these results indicate a shift to the right in the dose-response function for clonidine in prenatal EtOH-exposed offspring relative to control mice. Further, the results suggest that prenatal exposure to EtOH may result in long-lasting alterations in de veloping central NE systems, particularly presynaptic alpha(2) adrenor eceptor sensitivity.