Kathleen A. Grant
Alcohol abuse and alcoholism exact a tremendous toll on our society and is estimated by the Center for Disease Control to be the third largest preventable cause of death in the United States. On the other hand, a vast majority of regular alcohol drinkers never meet the criteria for alcoholism. Thus, there is an urgent need to understand who is at risk for developing alcoholism, how to detect early adverse biomedical consequences as the result of heavy drinking and how to develop a rationale approach to pharmacotherapeutic development aimed at decreasing harmful alcohol consumption.
Research in the Grant laboratory uses two fundamental paradigms in behavioral pharmacology to understand the risk for and consequences of heavy ethanol consumption. The first procedure is drug discrimination, in which the neural receptor basis for ethanol's subjective effects (i.e., the feelings associated with intoxication) is characterized. In these studies, the neurotransmitter systems that mediate the subjective feelings of intoxication in mice, rats, and monkeys are identified. Once identified, the lab determines if the intoxicating effects of ethanol are enhanced or antagonized by pharmacological pretreatment, genetic background, or organismal state (for example, stage of life, stress, menstrual cycle phase, etc.).
The second procedure is self-administration. In these studies, the addictive basis of ethanol is investigated in populations of monkeys to determine the influence of genetic composition, sex, age, and stress on the risk for heavy drinking. The consequences of heavy ethanol consumption are investigated with changes in functional genomics and proteomics, in vivo imaging with MRI/MRS, and endocrinological status. Along with this longitudinal approach, the lab has identified a combination of soluble proteins that serve as a sensitive marker for any alcohol use, as well as excessive alcohol use. These biomarkers can aid in clinical practice, helping to identify harmful drinking levels and adherence to abstinence programs.
Kathleen A. Grant is a Senior Scientist, and Head of the Division of Neuroscience at the ONPRC. She is also a Professor in the Department of Behavioral Neurosciences at OHSU. She earned her Ph.D. in Psychology from the University of Washington in 1984. This was followed by a 3-year postdoctoral fellowship at the University of Chicago. In 1987, she took an appointment as Staff Fellow at the National Institute on Alcohol Abuse and Alcoholism, becoming a Senior Staff Fellow in 1990. In 1991, she joined the faculty at Wake Forest University School of Medicine, where she remained until her appointment to the Center and OHSU in 2005.
KEY PUBLICATIONS (2014-2015)
Kroenke CD, Rohlfing T, Park B, Sullivan EV, Pfefferbaum A, Grant KA. Monkeys that voluntarily and chronically drink alcohol damage their brains: a longitudinal MRI study. Neuropsychopharmacology. 2014 Mar;39(4):823-30/ PMCID: PMC3924514.
Baker EJ, Farro J, Gonzales S, Helms C, Grant KA. Chronic alcohol self-administration in monkeys shows long-term quantity/frequency categorical stability. Alcohol Clin Exp Res. 2014 Nov;38(11):2835-43. doi: 10.1111/acer.12547. PMID: 25421519; PMCID: PMC4244650.
Pleil KE, Rinker JA, Lowery-Gionta EG, Mazzone CM, McCall NM, Kendra AM, Olson DP, Lowell BB, Grant KA, Thiele TE, Kash TL. NPY signaling inhibits extended amygdala CRF neurons to suppress binge alcohol drinking. Nat Neurosci. 2015 Mar 9. doi: 10.1038/nn.3972.[Epub ahead of print] PMID: 25751534; PMCID: PMC4376619.
Siciliano CA, Calipari ES, Cuzon-Carlson VC, Helms CM, Lovinger DM, Grant KA, Jones SR. Voluntary Ethanol Intake Predicts K-Opioid Receptor Supersensitivity and Regionally Distinct Dopaminergic Adaptations in Macaques. J Neurosci. 2015 Apr 15;35(15):5959-68. doi: 10.1523/JNEUROSCI.4820-15.2015. PMID 25878269.
See a full listing of Dr. Grant's publications.