title: Effects of prenatal ethanol exposure on later sensitivity to the low-dose stimulant actions of ethanol in mouse offspring: possible role of catecholamines.
abstract: The purpose of this study was to examine whether prenatal ethanol (EtOH) exposure alters later sensitivity to the low-dose stimulant effects of EtOH. Because the locomotor stimulant effects of EtOH are thought to be mediated, at least in part, by activation of brain monoamine systems, and because prenatal EtOH exposure has been shown to alter brain monoamine activity, it was hypothesized that prenatal EtOH exposure may alter sensitivity to the stimulant actions of EtOH. To test this hypothesis, sensitivity to the locomotor stimulant effects of various challenge doses of EtOH was examined in male and female offspring from prenatal alcohol (A), pair-fed (PF), and lab chow (LC) groups at different ages. In addition, to address the hypothesis further, sensitivity to the catecholamine synthesis inhibitor alpha-methyl-p-tyrosine (AMPT) was examined in these offspring, as well. Results indicated that male offspring prenatally exposed to EtOH exhibited reduced baseline activity and a blunted stimulant response to all challenge doses of EtOH (0.75-1.5 g/kg) in comparison with control offspring at 30 days of age, but these effects appeared to "normalize" at 70 days of age. Female EtOH-exposed offspring also exhibited a reduced baseline level of activity relative to control offspring, as well as a blunted stimulant response to the lowest challenge dose of EtOH (0.75 g/kg) at 30 days of age, and these effects persisted into adulthood. The stimulant response to higher doses of EtOH did not significantly differ among prenatal treatment groups in young or adult female offspring. However, because baseline activity was significantly lower in female EtOH-exposed offspring than control offspring, the stimulant response to these doses of EtOH (1.125 and 1.5 g/kg) was relatively greater than that for PF and LC offspring. Importantly, none of the differences in performance among the prenatal treatment groups could be attributed to an alteration in EtOH pharmacokinetics, because blood EtOH levels measured immediately following the 10-min test session were similar for all prenatal treatment groups across all of the EtOH test doses. Further, a similar response profile as that observed following EtOH challenge at 70 days of age was obtained following phenobarbital challenge (10-40 mg/kg). Finally, whereas AMPT (50-400 mg/kg) dose-dependently antagonized the stimulant effects of EtOH in all prenatal treatment groups, this effect of AMPT was significantly greater in mice prenatally exposed to EtOH in comparison with control offspring.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Ralph H. Johnson Veterans Administration Medical Center, Charleston, South Carolina.
authors.forename: H C
authors.initials: HC
authors.lastname: Becker
authors.forename: R L
authors.initials: RL
authors.lastname: Hale
authors.forename: W O
authors.initials: WO
authors.lastname: Boggan
authors.forename: C L
authors.initials: CL
authors.lastname: Randall
mesh_terms: D000367:Age Factors; D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D001143:Arousal / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D002395:Catecholamines / Q000502:physiology*; D000431:Ethanol / Q000493:pharmacokinetics; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology*; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D019805:alpha-Methyltyrosine
chemical_list: D002395:Catecholamines; D008781:Methyltyrosines; D000431:Ethanol; D019805:alpha-Methyltyrosine