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

Authors

  • Candice E. Van Skike,

    1. From the Department of Psychology and Neuroscience (CEVS, VSC, JV, JLD-G, DBM), Baylor University Addictions Research Consortium, Waco, Texas; Department of Neurosciences (PB, CFV), University of New Mexico School of Medicine, Albuquerque, New Mexico; Department of Psychology (ST, JMMD), The University of Memphis, Memphis, Tennessee; and Department of Psychology (DBM), Nanyang Technological University, Singapore.
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  • Paolo Botta,

    1. From the Department of Psychology and Neuroscience (CEVS, VSC, JV, JLD-G, DBM), Baylor University Addictions Research Consortium, Waco, Texas; Department of Neurosciences (PB, CFV), University of New Mexico School of Medicine, Albuquerque, New Mexico; Department of Psychology (ST, JMMD), The University of Memphis, Memphis, Tennessee; and Department of Psychology (DBM), Nanyang Technological University, Singapore.
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  • Vivien S. Chin,

    1. From the Department of Psychology and Neuroscience (CEVS, VSC, JV, JLD-G, DBM), Baylor University Addictions Research Consortium, Waco, Texas; Department of Neurosciences (PB, CFV), University of New Mexico School of Medicine, Albuquerque, New Mexico; Department of Psychology (ST, JMMD), The University of Memphis, Memphis, Tennessee; and Department of Psychology (DBM), Nanyang Technological University, Singapore.
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  • Sayaka Tokunaga,

    1. From the Department of Psychology and Neuroscience (CEVS, VSC, JV, JLD-G, DBM), Baylor University Addictions Research Consortium, Waco, Texas; Department of Neurosciences (PB, CFV), University of New Mexico School of Medicine, Albuquerque, New Mexico; Department of Psychology (ST, JMMD), The University of Memphis, Memphis, Tennessee; and Department of Psychology (DBM), Nanyang Technological University, Singapore.
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  • Janelle M. McDaniel,

    1. From the Department of Psychology and Neuroscience (CEVS, VSC, JV, JLD-G, DBM), Baylor University Addictions Research Consortium, Waco, Texas; Department of Neurosciences (PB, CFV), University of New Mexico School of Medicine, Albuquerque, New Mexico; Department of Psychology (ST, JMMD), The University of Memphis, Memphis, Tennessee; and Department of Psychology (DBM), Nanyang Technological University, Singapore.
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  • Jacob Venard,

    1. From the Department of Psychology and Neuroscience (CEVS, VSC, JV, JLD-G, DBM), Baylor University Addictions Research Consortium, Waco, Texas; Department of Neurosciences (PB, CFV), University of New Mexico School of Medicine, Albuquerque, New Mexico; Department of Psychology (ST, JMMD), The University of Memphis, Memphis, Tennessee; and Department of Psychology (DBM), Nanyang Technological University, Singapore.
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  • Jaime L. Diaz-Granados,

    1. From the Department of Psychology and Neuroscience (CEVS, VSC, JV, JLD-G, DBM), Baylor University Addictions Research Consortium, Waco, Texas; Department of Neurosciences (PB, CFV), University of New Mexico School of Medicine, Albuquerque, New Mexico; Department of Psychology (ST, JMMD), The University of Memphis, Memphis, Tennessee; and Department of Psychology (DBM), Nanyang Technological University, Singapore.
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  • C. Fernando Valenzuela,

    1. From the Department of Psychology and Neuroscience (CEVS, VSC, JV, JLD-G, DBM), Baylor University Addictions Research Consortium, Waco, Texas; Department of Neurosciences (PB, CFV), University of New Mexico School of Medicine, Albuquerque, New Mexico; Department of Psychology (ST, JMMD), The University of Memphis, Memphis, Tennessee; and Department of Psychology (DBM), Nanyang Technological University, Singapore.
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  • Douglas B. Matthews

    1. From the Department of Psychology and Neuroscience (CEVS, VSC, JV, JLD-G, DBM), Baylor University Addictions Research Consortium, Waco, Texas; Department of Neurosciences (PB, CFV), University of New Mexico School of Medicine, Albuquerque, New Mexico; Department of Psychology (ST, JMMD), The University of Memphis, Memphis, Tennessee; and Department of Psychology (DBM), Nanyang Technological University, Singapore.
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Reprint requests: Douglas B. Matthews, PhD, Department of Psychology, Nanyang Technological University, Singapore; Tel: 65 6592 1570; Fax: 65 6795 5797; E-mail: dmatthews@ntu.edu.sg

Abstract

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.

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