This laboratory uses different rodent models to study alcohol and cocaine addiction. The overall goal is the development of drugs or behavioral modifications that can serve as aids to the psychotherapy of alcoholism and drug addiction. A colony of selectively bred genetic drinking rats is used as the primary model of alcoholism in order to study the effects of potential drug treatments. Current experiments use a 10-day treatment of nicotine that covers the onset of puberty as a method to mimic the early onset use of drugs and then animals are studied as adults. Cocaine-induced place preference and bar pressing for intravenous cocaine self-administration through a jugular catheter in laboratory rats are used as the models to study manipulations of cocaine craving and consumption. Changes in brain neurotransmitters in tissues or in microdialysis samples taken while animals are behaving are measured by high performance liquid chromatography (HPLC) with carbon electrode detection. Radioligand methods are used to measure differences in the number or affinity of receptors for selected neurotransmitters. A collaboration with faculty in the Department of Psychology includes the use of operant chambers for food and liquid reinforcement of behavior. Through these experiments several promising drugs have been identified that have the potential to be of use in the treatment of addicted individuals.
McMillen, B. A., Joyner, P. W., Parmar, C. A., Tyer, W.E. & Williams, H.L., Effects of NMDA glutamate receptor antagonist drugs on the volitional consumption of ethanol by a genetic drinking rat. Brain Res. Bull.64:279-284, 2004.
Lucas, L.A.C. and McMillen, B.A. Effect of neuropeptide Y microinjected into the hypothalamus on ethanol consumption. Peptides25:2139-2145, 2004.
McMillen, B. A., Davis, B. J., Williams, H. L. and Soderstrom, K. Periadolescent nicotine exposure causes heterologous sensitization to cocaine reinforcement. Eur. J. Pharmacol. 509:161-164, 2005.
McMillen, B.A., Crawford, M.S., Kulers, C.M. and Williams, H.L. Effects of a metabotropic, mGlu5, glutamate receptor antagonist on ethanol consumption by genetic drinking rats. Alcohol & Alcoholism 40:494-497, 2005.
James-Walke, N. L., Williams, H. L., Taylor, D. A. and McMillen, B. A. The effect of oral consumption of perchlorate, alone and in combination with ethanol, on plasma thyroid hormone and brain catecholamine concentrations in the rat. Pharmacol. Toxicol. 99:340-345, 2006.
James-Walke, N. L., Williams, H. L., Taylor, D. A. and McMillen B. A., Periadolescent nicotine exposure produces sensitization to reinforcement by diazepam. Neurotoxicol. & Teratol. 29:31-36, 2007.
Soderstrom, K., Qin W., Williams, H. L., Taylor, D. A. and McMillen, B. A., Nicotine increases FosB expression within a subset of reward- and memory-related brain regions during both peri- and post-adolescence. Psychopharmacol.191:891-897, 2007.