title: Behavioral effects of ethanol in cerebellum are age dependent: potential system and molecular mechanisms.
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.
  
  
  METHODS
  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.
authors.affiliation: Department of Psychology and Neuroscience, Baylor University Addictions Research Consortium, Waco, Texas, USA.
authors.forename: Candice E
authors.initials: CE
authors.lastname: Van Skike
authors.forename: Paolo
authors.initials: P
authors.lastname: Botta
authors.forename: Vivien S
authors.initials: VS
authors.lastname: Chin
authors.forename: Sayaka
authors.initials: S
authors.lastname: Tokunaga
authors.forename: Janelle M
authors.initials: JM
authors.lastname: McDaniel
authors.forename: Jacob
authors.initials: J
authors.lastname: Venard
authors.forename: Jaime L
authors.initials: JL
authors.lastname: Diaz-Granados
authors.forename: C Fernando
authors.initials: CF
authors.lastname: Valenzuela
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Matthews
mesh_terms: D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000367:Age Factors; D000818:Animals; D001259:Ataxia / Q000139:chemically induced; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism*; D011689:Purkinje Cells / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000431:Ethanol; D011493:Protein Kinase C