Reduced sensitivity to the effects of clonidine on ethanol-stimulated locomotor activity in adult mouse offspring prenatally exposed to ethanol.
Prenatal exposure to ethanol (EtOH) alters developing catecholamine (CA) systems and acute sensitivity to the locomotor stimulant effects of EtOH. As an extension of previous work involving CA agents, this study addressed whether prenatal EtOH exposure influences central norepinephrine (NE) systems by examining the motoric effects of the direct alpha 2 adrenoreceptor agonist clonidine given alone and 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 (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 group were monitored for 10 minutes in an open field following IP injections 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 locomotor activity and attenuated the stimulant response to EtOH in a dose-dependent fashion. In contrast, clonidine given alone did not suppress, but appeared to stimulate, activity in prenatal EtOH-exposed offspring. Furthermore, the ability of clonidine to attenuate the locomotor stimulant properties of EtOH was greatly reduced in prenatal EtOH-exposed 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 developing central NE systems, particularly presynaptic alpha 2 adrenoreceptor sensitivity.
Weathersby
R T
RT
VA Medical Center, Research Service, Charleston, SC 29401.
Becker
H C
HC
Hale
R L
RL
D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009043:Motor Activity / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
D000431:Ethanol; D003000:Clonidine