Summary of Current Research
The broad area of interest in my laboratory is the genetic dissection of behavioral traits associated with 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, behavioral sensitivity, and neuroadaptation. We also examine traits that co-segregate with addiction. Mice genetically prone and resistant to the behavioral effects of abused drugs are used in pharmacological, genetic mapping, and gene expression studies to identify specific genetically-determined mechanisms that produce variations in addiction-related behavior. We are currently focusing most of our attention on two drugs, alcohol and methamphetamine, due to my involvement with both the Portland Alcohol Research Center (PARC) and Methamphetamine Abuse Research Center (MARC).
A primary interest is in mechanisms associated with alcohol and drug self-administration. The genetic studies in my lab have the potential to identify 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 are from studies that have focused on the peptide, corticotropin releasing factor (CRF), and more recently, on the trace amine-associated receptor 1 (TAAR1).
In addition to measuring behavior, pharmacological and molecular genetic approaches are utilized in my lab. For example, we used mice stereotactically implanted with indwelling cannulae to infuse drugs into specific brain regions or inactivate specific brain regions. We perform quantitative trait locus analysis for addiction-related traits and then interrogate possible underlying genes using immunohistochemistry, radioligand binding, and other approaches, with the input of research collaborators from other labs.
My lab is also very interested in the co-abuse of alcohol and nicotine and the role that nicotinic receptors and genes play in some alcohol effects. It is possible that these drugs are co-abused because there is a common underlying genetic mechanism in risk for addiction to the two drugs, because use of one drug with the other creates a stronger rewarding experience, or because one drug reduces some of the negative consequences of the other.These are hypotheses that we are exploring.
Finally, our primary research goal involving methamphetamine is to determine what genetic mechanisms impact risk for continued use of methamphetamine. To accomplish this, we are using selective breeding methods in combination with gene mapping and microarray gene expression analyses. We have completed the selective breeding of lines of mice that drink high and low amounts of methamphetamine and have found that the high line, compared to the low drinking line, shows increased sensitivity to the rewarding effects of methamphetamine, will work harder to gain access to a drinking tube that contains methamphetamine, and shows little sensitivity to aversive effects of methamphetamine. We have also found that neuroimmune pathways play a significant role in the differences between these high and low methamphetamine drinking lines, and that TAAR1 function plays a key role. We are collaborating with other investigators to develop novel pharmacotherapeutic agents for the treatment of methamphetamine addiction, and are also developing a model of binge-level methamphetamine use.
Postdoctoral Research Associate, Rutgers University
Assistant Professor, Department of Medical Psychology, OHSU
Associate Professor, Department of Behavioral Neuroscience, OHSU
Areas of interest
- Behavioral genetics
- Quantitative genetics
- B.A., William Paterson College 1981
- Ph.D., State University of New York, Albany 1986
Harkness JH, Shi X, Janowsky A, and Phillips TJ (2015) Trace amine-associated receptor 1 regulation of methamphetamine intake and related traits. Neuropsychopharmacology 40:2175-2184.
Gubner NR and Phillips TJ (2015) Effects of nicotine on ethanol-induced locomotor sensitization: A model of neuroadaptation. Behav Brain Res 288:26-32. PMCID:PMC4442015
Gubner NR, Cunningham CL and Phillips TJ (2015) Nicotine enhances the locomotor stimulating but not the conditioned rewarding effect of ethanol in DBA/2J mice. Alcohol Clin Exp Res 39:64-72. PMCID:PMC4312001
Lominac KD, McKenna CL, Schwartz LM, Ruiz PN, Wroten MG, Miller BW, Holloway JJ, Travis KO, Rajasekar G, Maliniak D, Thompson AB, Urman LW, Phillips TJ, and Szumlinski KK. (2014) Mesocorticolimbic monoamine correlates of methamphetamine sensitization and motivation. Front Syst Neurosci 8: article 70 (19 pages) PMCID:PMC4019853
Eastwood EC, Barkley-Levenson AM, and Phillips TJ. (2014) Methamphetamine drinking microstructure in mice bred to drink high or low amounts of methamphetamine. Behav Brain Res 272:111-120. PMCID:PMC4167388
Eastwood EC and Phillips TJ (2014) Morphine intake and the effects of naltrexone and buprenorphine on the acquisition of methamphetamine intake. Genes Brain Behav 13:226-235. PMCID: PMC3976242