Office: 317-274-0194
Fax: 317-274-1365
Email: ngrahame@iupui.edu
With a long term goal of better understanding the causes of heritable alcoholism, my laboratory focuses on the behavioral and physiological determinants of genetic differences in alcohol drinking in mice, using modern genetic models such as selected lines and targeted mutations. Mice are ideal for understanding genetic differences in alcohol’s rewarding effects because on a molecular genetic level, they are well-characterized, and they drink alcohol readily. I have also studied their ability to acquire intravenous self-administration of alcohol (indicating that taste alone is not the reason they drink), their preference for locations in which alcohol was administered, and their increased sensitivity to alcohol’s locomotor activating effects following alcohol experience. Working with selected lines of High and Low-Alcohol Preferring mice, I have found that high drinking animals become more sensitive to alcohol’s activating effects than the low-drinking mice, consistent with theories about some of the causes of drug dependency as well as data from human familial studies. Additionally, High- Alcohol Preferring mice are less likely to show alcohol withdrawal. Presently, my lab is defining new, reliable procedures to assess alcohol’s rewarding and aversive effects in mice. I am also working with Dr. William McBride to develop neurochemical data on the selected lines. These assays can then be used for pharmacological and genetic characterization of the causes of high alcohol intake in these animals. Overall, by using rigorous behavioral and physiological testing procedures, these studies seek to better understand the causes of genetic differences in alcohol drinking.
Recent Publications:
Bachtell, R.K., Weitemier, A.Z., Galvan-Rosas, A.,
Tsivkovskaia, N.O., Risinger, F.O., Phillips, T.J., Grahame, N.J., and Ryabinin,
A.E. (2003). The Edinger-Westphal-Lateral Septum Urocortin pathway and its
relationship to alcohol consumption. Journal of Neuroscience, 23,
2477-2487.
Grahame, N.J., Cunningham, C.L. (2002).
Intravenous Self- Administration of ethanol in the mouse. Current Protocols
in Neuroscience Supplement 19, Unit 9.11.1-9.11.19.
Chester, J.A., Lumeng, L., Li, T-K., and Grahame,
N.J. (2002). High and Low Alcohol-Preferring Mice Show Differences in
Conditioned Taste Aversion to Alcohol. Alcoholism: Clinical and
Experimental Research 27, 12-18.
Grahame, N.J. (2000). Hunt for the Genes Involved in
Alcoholism: Strain Differences and Selective Breeding. Alcohol Health and
Research World 23,159-163.
Grahame, N.J., Rodd-Henricks K., Li, T.-K., and
Lumeng, L. (2000). Ethanol Locomotor Sensitization, but not Tolerance
Correlates with Selection for Alcohol Preference in High- and Low-Alcohol
Preferring Mice. Psychopharmacology, 151, 252-260.