PRINCIPAL INVESTIGATORS

Roy A. Wise, Ph.D., F.R.S.C., Senior Investigator

Chief, Behavioral Neuroscience Section

Ph.D. - McGill University (thesis advisor: Dalbir Bindra)

B.A., M.A., - California State University

RESEARCH INTERESTS

My interest is in the brain mechanisms of motivation and addiction. Our current studies focus on the mesolimbic and nigrostriatal dopamine systems, systems that appear to stamp in or "reinforce" stimulus-stimulus, stimulus-response, and response-outcome learning involved in habit formation. These systems are activated by addictive drugs, unexpected rewards, and reward predictors, and they are modified by experience with drugs of abuse. We are interested in the neuronal inputs that carry reward-predictive signals and we are interested in drug-induced modifications that, for example, change the sensitivity of the system to stress. Our current studies are based on microdialysis studies of intravenous drug self-administration and involve interdisciplinary collaborations involving histochemistry, electrophysiology, in vivo voltammetry, and cell biology. Of particular interest are manipulations of the glutamatergic, cholinergic, and CRF inputs to the ventral tegmental area using receptor-specific neurotoxins, small interfering RNA, and viral overexpression of the glutamate-1 transporter.

Selected Publications:

1. Wise, R. A. (2009). Roles for nigrostriatal—not just mesocorticolimbic—dopamine in reward and addiction. Trends in Neurosciences, 32, 517-524.

2. You Z.B., Wang B., Zitzman D., Azari S., Wise R.A. (2008). Acetylcholine release in the mesocorticoloimbic dopamine system during cocaine seeking: conditioned and unconditioned contributions to reward and motivation. Journal of Neuroscience, 28, 9021-9029.

3. Wise R.A., Wang B., You Z.B. (2008). Cocaine serves as a peripheral interoceptive conditioned stimulus for central glutamate and dopamine release. PLoS One, 3, e2846.

4. Geisler S., Wise R.A. (2008). Functional implications of glutamatergic projections to the ventral tegmental area. Reviews in the Neurosciences, 19, 227-244.

5. You Z.B., Wang B., Zitzman D., Azari S., Wise R.A. (2007). A role for conditioned ventral tegmental glutamate release in cocaine-seeking. Journal of Neuroscience, 27, 10546-10555.

6. Wang B., Shaham Y., Zitzman D., Azari S., Wise R.A., You Z.B. (2005). Cocaine experience establishes control of midbrain glutamate and dopamine by corticotropin-releasing factor: a role in stress-induced relapse to drug-seeking. Journal of Neuroscience, 25, 5389-5396.

7. Wise R.A. (2004). Dopamine, learning and motivation. Nature Reviews Neuroscience, 5, 483-494.

8. Wise R.A. (2004). Drive, incentive, and reinforcement: The antecedents and consequences of motivation. Nebraska Symposium on Motivation, 50, 159-195.

9. Wise R.A. (1989). The brain and reward. In JM Liebman and SJ Cooper (Eds.) The Neuropharmacological Basis of Reward. Oxford: Oxford University Press, pp. 377-424.

10. Wise R.A. (1987). Intravenous drug self-administration: A special case of positive reinforcement. In MA Bozarth (Ed.) Methods of Assessing the Reinforcing Properties of Abused Drugs. New York: Springer-Verlag, pp. 117-141.

11. Wise R.A. (1987). Sensorimotor modulation and the variable action pattern (VAP): Toward a noncircular definition of drive and motivation. Psychobiology, 15, 7-20.