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 Professor, 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 (2015-2016)
Turecek J, Han VZ, Cuzon Carlson VC, Grant KA, Welsh JP. Electrical Coupling and Synchronized Subthreshold Oscillations in the Inferior Olive of the Rhesus Macaque. J Neurosci. 2016 Jun 15;36(24):6497-502.
Siciliano CA, Calipari ES,Yorgason JT, Lovinger DM, Mateo Y, Jimenez VA, Helms CM, Grant KA, Jones SR.Increased presynaptic regulation of dopamine neurotransmission in the nucleus accumbens core following chronic ethanol self-administration in female macaques. Psychopharmacology (Berl). 2016 Apr;233(8):1435-43.
Beattie MC, Maldonado-Devincci AM, Porcu P, O'Buckley TK, Daunais JB, Grant KA, Morrow AL.Voluntary ethanol consumption reduces GABAergic neuroactive steroid (3α,5α)3-hydroxy pregnan-20-one (3α,5α-THP) in the amygdala of the cynomolgus monkey. Addict Biol. 2015 Dec 2. doi: 10.1111/adb.12326.
Jimenez VA, Helms CM,Cornea A, Meshul CK, Grant KA. An ultrastructural analysis of the effects ofethanol self-administration on the hypothalamic paraventricular nucleus in rhesus macaques. Front Cell Neurosci. 2015 Jul 14;9:260. doi:10.3389/fncel.2015.00260. eCollection 2015.
Siciliano CA, Calipari ES, Cuzon Carlson VC, Helms CM, Lovinger DM, Grant KA, Jones SR. Voluntary ethanolintake predicts κ-opioid receptor supersensitivity and regionally distinct dopaminergic adaptations in macaques. J Neurosci. 2015 Apr 15;35(15):5959-68.doi: 10.1523/JNEUROSCI.4820-14.2015.
See a full listing of Dr. Grant's publications.