Behavioral Effects of Ethanol in Cerebellum Are Age Dependent: Potential System and Molecular Mechanisms

• Published in: Alcoholism, clinical and experimental research clinical and experimental research, 2010-12, Vol.34 (12), p.2070-2080
• Main Authors: Van Skike, Candice E., Botta, Paolo, Chin, Vivien S., Tokunaga, Sayaka, McDaniel, Janelle M., Venard, Jacob, Diaz-Granados, Jaime L., Valenzuela, C. Fernando, Matthews, Douglas B.
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Adolescence; Age; Age Factors; Alcoholism; Alcoholism and acute alcohol poisoning; Animals; Ataxia; Ataxia - chemically induced; Biological and medical sciences; Blood; Brain; Cerebellum; Cerebellum - drug effects; Cerebellum - metabolism; Cerebellum - physiology; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Cortex; Cortex (motor); Drug abuse; Electrophysiological recording; Ethanol; Ethanol - blood; Ethanol - pharmacology; Firing rate; Hippocampus - drug effects; Hippocampus - metabolism; Male; Medical sciences; Membrane Potentials - drug effects; Membrane Potentials - physiology; Molecular modelling; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; PKC Gamma; Protein kinase C; Protein Kinase C - metabolism; Purkinje; Purkinje cells; Purkinje Cells - physiology; Rats; Rats, Sprague-Dawley; Toxicology
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/j.1530-0277.2010.01303.x

Background:  Adolescent rats are less sensitive to the motor‐impairing effects of ethanol than adults. However, the cellular and molecular mechanisms underlying this age‐dependent effect of ethanol have yet to be fully elucidated. Method:  Male rats of various ages were used to investigate ethanol‐induced ataxia and its underlying cellular correlates. In addition, Purkinje neurons from adolescent and adult rats were recorded both in vivo and in vitro. Finally, protein kinase C (PKCγ) expression was determined in 3 brain regions in both adolescent and adult rats. Results:  The present multi‐methodological investigation confirms that adolescents are less sensitive to the motor‐impairing effects of ethanol, and this differential effect is not because of differential blood ethanol levels. In addition, we identify a particular cellular correlate that may underlie the reduced motor impairment. Specifically, the in vivo firing rate of cerebellar Purkinje neurons recorded from adolescent rats was insensitive to an acute ethanol challenge, while the firing rate of adult cerebellar Purkinje neurons was significantly depressed. Finally, it is demonstrated that PKCγ expression in the cortex and cerebellum mirrors the age‐dependent effect of ethanol: adolescents have significantly less PKCγ expression compared to adults. Conclusions:  Adolescents are less sensitive than adults to the motor‐impairing effects of ethanol, and a similar effect is seen with in vivo electrophysiological recordings of cerebellar Purkinje neurons. While still under investigation, PKCγ expression mirrors the age effect of ethanol and may contribute to the age‐dependent differences in the ataxic effects of ethanol.