An investigation of the behavioral actions of ethanol across adolescence in mice.
BACKGROUND
The transition from adolescence into adulthood is characterized by rapid maturation of brain systems mediating reward and by increasing experimentation with drugs of abuse including ethanol (EtOH). Previous studies have found marked differences in sensitivity to the behavioral effects of EtOH in adolescent rats as compared to adults, but relatively few studies have been conducted in mice.


OBJECTIVE
The present study examined sensitivity to various behavioral effects of EtOH in C57BL/6J mice at various stages of adolescence/adulthood (4, 6, 8 weeks old). Ages were compared for locomotor stimulant (open field), anxiolytic-like (elevated plus-maze), memory-impairing (Pavlovian fear conditioning) and ataxic (accelerating rotarod) effects of EtOH, and the sedative/hypnotic (sleep time) effects of EtOH and pentobarbital. EtOH self-administration was compared using a two-bottle choice paradigm. Measures of EtOH metabolism were also obtained.


RESULTS
Early adolescent mice exhibited increased sensitivity to locomotor stimulant (1.5 g/kg), anxiolytic-like (1.5 g/kg) and ataxic (1.5-2.5 g/kg), but not memory impairing (2.0 g/kg), effects of EtOH relative to adults. Early adolescent, and to some extent peri-adolescent, mice were less sensitive than adults to the sedative/hypnotic effects of EtOH (3.5-4.5 g/kg), but not pentobarbital (40-50 mg/kg). Early adolescent mice showed lower EtOH preference, but not EtOH consumption, than adults. Blood EtOH concentrations were higher at early time points and lower at later time points after (3.0 g/kg) EtOH injection in early and peri-adolescents relative to adults.


CONCLUSIONS
Present data demonstrate that sensitivity to the acute intoxicating effects of EtOH changes across mouse adolescent development in a behavior-dependent manner.
Hefner
Kathryn
K
Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institute of Mental Health, 5625 Fishers Lane Rm 2N09, Rockville, MD 20852-9411, USA.
Holmes
Andrew
A
D000367:Age Factors; D000428:Alcohol Drinking; D000704:Analysis of Variance; D000818:Animals; D001259:Ataxia / Q000139:chemically induced; D001522:Behavior, Animal / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology; D012646:Self Administration; D012890:Sleep / Q000187:drug effects
D002492:Central Nervous System Depressants; D000431:Ethanol; D010424:Pentobarbital