Graduate Studies Faculty

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Profile

Major Areas

• Behavioral genetics
• Quantitative genetics
• Drug and alcohol addiction

  Summary of Current Research

  The broad area of interest in my laboratory is the genetic dissection of behavioral traits thought to influence risk for the development of alcoholism and drug abuse. We utilize genetic animal models to study acute and chronic drug and alcohol effects associated with drug reward and behavioral sensitivity. In collaboration with other investigators, we also examine traits that co-segregate with addiction, like impulsivity. Mice genetically prone and resistant to the behavioral effects of abused drugs are used in pharmacological and genetic mapping studies to identify specific neurotransmitter systems and chromosomal locations of genes that produce variations in behavior. We are currently focusing most of our attention on two drugs, alcohol and methamphetamine due to my invovlement with both the Portland Alcohol Research Center (PARC) and Methamphetamine Abuse Research Center (MARC).
  
  A primary interest is the mechanisms of behavioral sensitization (i.e., the increase in the effect of a drug with repeated exposures). The neuroadaptations associated with behavioral sensitization have been proposed to be determinant factors in the development of drug addiction; they may be associated with the transition from casual use to excessive use and addiction. The genetic studies in my lab have the potential for identifying common and unique genetic and neurochemical mechanisms underlying the motivational and neuroadaptive effects of addictive drugs. Genetic models we use include selectively bred mouse lines, panels of inbred strains, transgenic mice, knockout mice, recombinant inbred strains, and congenic strains. Some of our most exciting results focused on the peptide, corticotrophin releasing factor (CRF), and were published in PNAS in 2008.
  
  

  Pharmacological and molecular genetic approaches are utilized. For example, we used mice stereotactically implanted with indwelling cannulae to infuse drugs into the ventral tegmental area (VTA), and found that GABA-B receptors are involved in determining sensitivity to alcohol's stimulant effects. Sensitivity to the behaviorally stimulating effects of alcohol may be predictive of risk for the development of alcoholism. We have also obtained strong support for a common genetic locus on mouse chromosome 9 that influences alcohol locomotor stimulation and self-administration, as well as methamphetamine-induced stimulation. Finer mapping is currently underway to narrow the region to one containing few genes for further study.
  
  

  Our primary research examining issues important to methamphetamine abuse involve a direct examination of the genetic relationship between sensitization and self-administration. To accomplish this we are using selective breeding methods in combination with gene mapping and microarray gene expression analyses. We have completed the selection of lines that drink high and low amounts of methamphetamine and have found that the high line shows increaed sensitivity to methamphetamin-induced conditioned place preference (a measure of reward) and reduced sensitivity to methamphetamin-induced conditioned taste aversion (a measure of aversion).
  
  

  Recent Publications

  Beckstead, M.J. and Phillips, T.J. (2009) Mice selectively bred for high or low alcohol-induced locomotion exhibit differences in dopamine neuron function. J Pharmacol Exp Therap 329:342-349. 

  Holstein, S.E., Dobbs, L., Phillips, T.J. (2009) Attenuation of the stimulant response to ethanol is associated with enhanced ataxia for a GABA_A, but not a GABA_B, receptor agonist. Alcohol Clin Exp Res 33:108-120.

  Meyer, P.J., Meshul, C.K. and Phillips, T.J. (2009) Ethanol- and cocaine-induced locomotion are genetically related to increases in accumbal dopamine. Genes Brain Behavior 8:346-355.
  

  Scibelli, A.C. and Phillips, T.J. (2009) Combined scopolamine and ethanol treatment results in a synergistic locomotor stimulant response not blocked by dopamine receptor antagonists. Alcohol Clin Exp Res 33:435-447.
  

  Education

  • B.A. (1981) William Paterson College
  • Ph.D. (1986) State University of New York, Albany

  Previous Positions

  • Postdoctoral Research Associate, Rutgers University
  • Assistant Professor, Department of Medical Psychology, OHSU
  • Associate Professor, Department of Behavioral Neuroscience, OHSU

  Non-Academic Interests

  • Tennis