PRINCIPAL INVESTIGATORS

Carl R. Lupica, Ph.D., Senior Investigator

Chief, Electrophysiology Research Section

Post-doctoral Training - 1989-1991, Neuropharmacology, University of Colorado College of Medicine; Advisor: Thomas V. Dunwiddie

Ph.D. - 1989, Psychobiology, Wayne State University. Detroit, MI

M.A. - 1986, Psychobiology, Wayne State University. Detroit, MI

B.A. - 1983, Psychology/Zoology, Ohio University, Athens, OH

RESEARCH INTERESTS

The research in my laboratory is primarily focused upon determining the acute mechanisms through which abused drugs alter neuronal activity in the brain. In addition, we are interested in the long-term adaptations that occur within brain circuits that result from prolonged exposure to abused drugs such as Δ⁹-tetrahydrocannabinol (THC), the primary psychoactive constituent of marijuana. The primary experimental approach used in the laboratory is electrophysiology, including single neuron recordings in brain slices, intact animals, and in cultured and acutely dissociated cells. We also use carbon fiber electrodes to measure monoamines such as dopamine (DA), serotonin (5-HT), and norepinephrine (NE) in brain slices. Since the focus of NIDA is on the understanding of drug abuse and addiction, we utilize several brain slice preparations that preserve components of the brain's reward circuitry that represent a shared target of these abused drugs. Thus, brain slices containing the ventral tegmental area (VTA) and nucleus accumbens (NAc) are used routinely in the laboratory. However, we are also interested in the mechanisms in which abused drugs affect cognition and drug craving and therefore utilize acute preparations of a brain area involved in learning and memory known as the hippocampus. Many of our studies also incorporate genetically modified animals so that the molecular sites of drug interaction can be conclusively identified. It is hoped that our contribution to understanding how abused drugs affect the brain will lead to effective future treatments for compulsive drug use and addiction.

Selected Publications:

1. Good, C. H. & Lupica, C. R. (2009). Properties of distinct ventral tegmental area synapses activated via pedunculopontine or ventral tegmental area stimulation in vitro. Journal of Physiology, 587, 1233-1247.

2. Li, X., Hoffman, A.F., Peng, X.Q., Lupica, C. R., Gardner, E.L., & Xi, Z. X. (2009). Attenuation of basal and cocaine-enhanced locomotion and nucleus accumbens dopamine in cannabinoid CB1-receptor-knockout mice. Psychopharmacology, 204, 1-11.

3. Freed, W.J., Chen, J., Bäckman, C.M., Schwartz, C.M., Vazin, T., Cai, J., et al. (2008). Gene expression profile of neuronal progenitor cells derived from hESCs: activation of chromosome 11p15.5 and comparison to human dopaminergic neurons. PLoS ONE, 3, e1422, doi:10.1371/journal.pone.0001422.

4. Chen, Y. H., Harvey, B.K., Hoffman, A.F., Wang, Y., Chiang, Y. H, & Lupica, C. R. (2008). MPTP-induced deficits in striatal synaptic plasticity are prevented by glial cell line-derived neurotrophic factor expressed via an adeno-associated viral vector, FASEB Journal, 22, 261-275.

5. Spivak, C.E., Lupica, C. R., & Oz, M. (2007). The endocannabinoid anandamide inhibits the function of α4ß2 nicotinic acetylcholine receptors. Molecular Pharmacology, 72, 1024–1032.

6. Hoffman, A.F. Oz, M., Yang, R., Lichtman, A., & Lupica, C. R. (2007). Opposing actions of chronic Δ⁹-tetrahydrocannabinol and cannabinoid antagonists on hippocampal long-term potentiation. Learning & Memory, 14, 63-74.

7. Hoffman, A.F., Macgill, A.M., Smith, D., Oz, M., & Lupica, C. R. (2005). Species and strain differences in the expression of a novel glutamate-modulating cannabinoid receptor in the rodent hippocampus. European Journal of Neuroscience, 22, 2387-2391.

8. Lupica, C. R. &. Riegel, A.C. (2005). Endocannabinoid release from midbrain dopamine neurons: a potential substrate for cannabinoid receptor antagonist treatment of addiction. Neuropharmacology, 48, 1105-1116.

9. Riegel, A.C. & Lupica, C. R. (2004). Independent presynaptic and postsynaptic mechanisms regulate endocannabinoid signaling at multiple synapses in the ventral tegmental area. The Journal of Neuroscience, 24, 11070-11078.

10. Hoffman, A.F. & Lupica, C. R. (2000). Mechanisms of cannabinoid inhibition of GABAA synaptic transmission in the hippocampus. The Journal of Neuroscience, 20, 2470-2479.