Studies in the laboratory concentrate on the neurobiology of addiction. Our experiments range from the analysis of behavior to the study of receptor trafficking. For our research on nicotine addiction we use in vivo telemetry to measure physiological parameters while rodents conduct drug-influenced behavioral tasks. These in vivo studies are supported by in vitro research using a wide range of molecular and cell biological techniques to dissect the mechanistic events that give rise to the behavioral results. We are particularly interested in the interaction between stress and nicotine, as smokers often report an anxiolytic effect of cigarettes, and stress-related disorders such as depression, PTSD, and anxiety are often associated with chronic nicotine use. The stress/nicotine interaction is also analyzed with respect to the influence of gender.
Our studies naturally extend to the molecular mechanisms of withdrawal because anxiogenic responses are an important component of the nicotine withdrawal syndrome. Experiments are conducted on mice lacking one or combinations of neuronal nicotinic receptor subunits, mice overexpressing the stress-related isoform of the human enzyme acetylcholinesterase, and mice lacking one or both isoforms of the progesterone receptor. Other studies conducted in the lab focus on the effects of nicotine on nicotinic receptor trafficking. Nicotine's regulation of receptor trafficking may affect the number of nicotinic receptors at the plasma membrane and consequently influence synaptic plasticity. In that way, nicotine-induced changes in trafficking and degradation could contribute to nicotine addiction. Current experiments are testing the hypothesis that nicotine alters nicotinic receptors trafficking by affecting their interaction with the ubiquitin/proteasome system. These studies have implications not only for the role of nicotine in addiction but also for its effects on whole body physiology.
K Rezvani, Y Teng, Y. Pan, J Lindstrom, JM McIntosh, JA Dani, M. De Biasi. The UBX-containing protein UBXD4 regulates cell surface number and subunit stability of a3* nicotinic acetylcholine receptors. J. Neuroscience (under revision).
D. Gangitano, R. Salas, E. Perez, Y. Teng, M. De Biasi. Gender-specific effects of the a5 nicotinic receptor subunit on anxiety- and depression-like behaviors. Genes, Brain & Behavior (under revision).
R. Salas, A. Main, D.A. Gangitano, M. De Biasi. Chronic stress facilitates behavioral sensitization to nicotine and mitigates nicotine-induced hypolocomotion. Neuropsychopharmacology (under revision).
R. Salas, A. Main, D.A. Gangitano, H. Soreq, M. De Biasi (2008). Chronic nicotine relieves anxiogenic-like behavior in transgenic mice carrying the human Acetylcholinesterase-R gene. Molecular Pharmacology (accepted).
M. De Biasi & R. Salas. Influence of neuronal nicotinic subunits over nicotine addiction and withdrawal (2008). Experimental Biology & Medicine (in press).
R. Salas & M. De Biasi (2008). Opposing actions of chronic stress and chronic nicotine on striatal function in mice. Neuroscience Letters 440(1):32-4.
R. Salas, A. Main, D. Gangitano, M. De Biasi (2007). Decreased withdrawal symptoms but normal tolerance to nicotine in mice null for the a7 nicotinic acetylcholine receptor subunit. Neuropharmacology 53: 863-869.
K. Rezvani, Y. Teng, D. Shim, M. De Biasi (2007). Nicotine regulates multiple synaptic proteins by inhibiting proteasomal activity. J. Neuroscience 27(39): 10508-19.
F.M. Zhou, Y. Liang, R. Salas, Li. Zhang, M. De Biasi, J. A. Dani (2005). Co-release of Dopamine and Serotonin from Striatal Dopamine Terminals. Neuron 46:65-74.
Y. Liang , R. Salas , L. Marubio, D. Berkovich, M. De Biasi, A.L. Beaudet, JA Dani (2004). Functional polymorphisms in the human beta4 subunit of nicotinic acetylcholine receptors. Neurogenetics 5(1):1007-10026.
Awards, Recognition, Appointments, and Honors
Lyndon B. Johnson Award for most outstanding research project funded by the American Heart Association - TX Affiliate.
Distinguished Lecturer: American Society for Peripheral Nerve. Los Angeles, June 19-21, 1999.
Wiersma Visiting Professor, Caltech, Pasadena, February 3-9, 2003.
Current Graduate Students
- Dang Dao (Neuroscience)
- Edwin Alexander (Neuroscience)
- Erika Perez (Neuroscience)