Lukas will use the $965,000 grant, given by a private foundation, for studies of chemical signaling molecules that may be particularly relevant to nicotine reward and dependence. Nicotinic acetylcholine receptors present in the pleasure-reward centers of the brain are the likely mediators of nicotine's rewarding effects that lead to dependence. One form of nicotinic receptor, while poorly understood, is thought to be most dense in these brain centers. Dr. Lukas and his colleague at Barrow, Dr. Jie Wu, will lead studies of the structure, function and localization of these nicotinic receptors.
The second study, funded by a $4.6 million grant from the NIH, establishes Barrow as a site involved in a National Cooperative Drug Discovery Group charged with identification leading to the development of novel drug treatments for nicotine dependence. The research team will follow on the observation made initially in Lukas' laboratory that the anti-depressant and smoking cessation aid, bupropion (also known as Wellbutrin and Zyban), has actions at nicotinic receptors that seem to mimic those of long-term exposure to nicotine.
Drugs related to bupropion will be synthesized, studied for their effects at nicotinic receptors and other molecular targets, and examined for their effects on measures of nicotine dependence. Drugs with the desired properties will be candidates for clinical trials for depression and to aid smoking cessation.
Other participants in the NIH study include investigators at Virginia Commonwealth University in Richmond, the Research Triangle Institute in North Carolina and the NIH. Lukas' laboratory has been conducting basic research of clinical relevance on nicotinic receptors for nearly 25 years at Barrow.