Sensitivity and Tolerance to the Hypnotic and Ataxic Effects of Ethanol in Adolescent and Adult C57BL/6J and DBA/2J Mice

• Published in: Alcoholism, clinical and experimental research clinical and experimental research, 2009-03, Vol.33 (3), p.464-476
• Main Authors: Linsenbardt, David N., Moore, Eileen M., Gross, Carly D., Goldfarb, Karen J., Blackman, Laverne C., Boehm II, Stephen L.
• Format: Article
• Language: English
• Subjects: Adolescent; Age Factors; Alcohol; Alcoholism and acute alcohol poisoning; Animals; Ataxia; Ataxia - chemically induced; Biological and medical sciences; Central Nervous System Depressants - adverse effects; Central Nervous System Depressants - pharmacokinetics; Drug Tolerance; Ethanol - adverse effects; Ethanol - blood; Ethanol - pharmacokinetics; Female; Loss of Righting Reflex; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Motor Activity - drug effects; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Tolerance; Toxicology
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/j.1530-0277.2008.00857.x

Background:  There is considerable research examining differences in adolescent and adult sensitivity and tolerance to ethanol related behavioral phenotypes. However, the available published data has almost exclusively assessed these behaviors in outbred rats. The present study was conducted using the alcohol preferring inbred mouse strain C57BL/6J (B6) and the alcohol nonpreferring inbred mouse strain DBA/2J (D2) to determine if differences in the sedative and ataxic effects of ethanol exist between adolescents and adults, and to determine whether there are any genetic influences involved therein. Methods:  Adolescent and adult mice of each sex and genotype were given intraperitoneal (i.p.) injections of ethanol (1.5, 1.75, or 4.0 g/kg) or saline and assessed for the loss of righting reflex (LORR) or hind footslips on the balance beam apparatus. These animals were then tested for the development of tolerance to these behaviors on subsequent days. Results:  Despite evident pharmacokinetic differences, D2 adolescents were found to be relatively less sensitive to ethanol’s hypnotic actions than their adult D2 counterparts. Adolescent and adult B6 animals did not differ. Furthermore, although adult animals appeared to develop significantly greater degrees of tolerance to ethanol‐induced hypnosis compared with adolescents, these effects were likely in part related to differences in ethanol absorption/metabolism across time. Taking into account pharmacokinetic differences and the overall poor performance of male adults, adolescent animals were found to be equally if not more sensitive to the motor incoordinating (ataxic) effects of ethanol. Overall, tolerance to these effects varied by age and genotype but appeared to be related to changes in ethanol pharmacokinetics rather than strict behavioral sensitivity. Conclusion:  The current work suggests that adolescent B6 and D2 inbred mice exhibit ontogenetic differences in sensitivity to ethanol’s hypnotic and ataxic effects. Importantly, in some cases age differences emerge as a function of differential ethanol pharmacokinetics. These results extend the current literature examining this critical developmental period in mice and illustrate the benefits of comparing ethanol related developmental differences in different genetic mouse populations.