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The challenge of current and future studies in the Roberto laboratory is to understand which specific neuronal mechanisms underlie synaptic and/or molecular changes that influence the development of drug addiction and alcohol dependence. Alcohol abuse causes 4% of the global disease burden, and accounts for extensive unmet medical needs. With prolonged alcohol abuse, adaptations occur at the cellular level as the brain attempts to overcome the acute effects of alcohol intake. Often, these adaptations lead to long-term changes in the structure and function of neurons. The synapse is the primary point for information transfer between neurons, and a central hypothesis of alcohol research is that synapses are the most sensitive sites of alcohol action. Thus, our laboratory focuses on the synapses of the central nucleus of the amygdala, a brain region considered to be crucial in mediating the behavioral effects of acute and chronic drug consumption. Our aim is to understand the effects and interactions of neuropeptides and alcohol on neuronal function and synaptic transmission using electrophysiological, pharmacological, and molecular methods. The discovery and characterization of such neuroadaptative changes has been, and will continue to be, useful toward developing new therapeutic agents to alleviate drug dependence, particularly alcohol dependence.
Publications:
Roberto M., Madamba S., Moore S.D., Tallent M.K. and Siggins G.R. (2003) Ethanol increases GABAergic transmission at both pre- and postsynaptic sites in rat central amygdala neurons. Proceedings of National Academy of Sciences USA 100:4, 2053-2058.
Roberto M., Gilpin N., O’Dell L.E., Cruz M.T., Morse A.C., Siggins G.R. and Koob G.F. (2008) Cellular and behavioral rationale for GABApentin treatment of alcohol dependence. Journal of Neuroscience 28 (22): 5762-5771.
Roberto M., Cruz M.T., Gilpin N.W., Sabino V., Schweitzer P., Bajo M., Cottone P., Madamba S.M, Stouffer D.G., Zorrilla E.P., Koob G.F., Siggins G.R, Parsons L.H. (2010) Amygdala GABA release and CRF: Key mediators of alcohol dependence. Biological Psychiatry 67(9):831-9.
Roberto M. and Siggins G.R. (2006) Nociceptin/orphanin FQ presynaptically decreases
GABAergic transmission and blocks the ethanol-induced increase of GABA release in central amygdala. Proceedings of National Academy of Sciences USA 103: 9715-9721.
Bajo M., Cruz M.T., Siggins G.R., Messing R. and Roberto M. (2008) Protein kinase C epsilon mediation of CRF- and ethanol-induced GABA release in central amygdala. Proceedings of National Academy of Sciences USA, 17;105(24):8410-5. |
