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Faculty
Research Interests The dopaminergic cells of the ventral tegmental area and substantia nigra pars compacta are part of a well-established pathway that regulates goal-directed and reward-seeking behaviors, and are the principal cells affected in pathological conditions such as Parkinson's Disease and addiction. Many drugs of abuse exert dysregulating effects on brain levels of dopamine and other neurotransmitters, which then have widespread effects on the firing patterns of dopamine neurons. One key mechanism by which psychostimulant drugs (most notably, cocaine and amphetamine) exert their effect is by altering interactions among multiple receptor subtypes (e.g., adrenergic, glutamatergic, GABAergic, and cholinergic) that are co-expressed on dopamine neurons. Changes in receptor interactions and their resultant effect on dopamine neuron activity may underlie many of the behavioral changes associated with drug addiction, and these alterations may be independent from the natural reward seeking mechanisms like feeding behavior. My research uses two broad approaches to study dopamine system physiology: 1) direct manipulation of receptor interactions on individual dopamine neurons in vivo and in vitro to investigate normal physiology and function; and 2) behaviorally-induced changes of receptor interactions via drug self-administration assays, which will determine the causal relationship between altered receptor interactions and drug-seeking behaviors. To achieve the first goal, we measure physiological responses (i.e., current, voltage and calcium fluxes) of dopamine neurons to electrophysiological stimulation and direct application of pharmacological agents. For the second goal, we use behavioral measures and electrophysiological techniques in tandem. First, we measure drug-taking behavior in the presence of intravenous or intracranial pharmacological agents, and then assay the dopamine neurons in vitro. Through combined electrophysiological, imaging, pharmacological, and behavioral methods we investigate dopamine neuron function to arrive at the functional contribution of this system in both normal and pathological states.
Selected Publications: Paladini C. A., Mitchell J. M., Mark G. P., and Williams J. T.; Cocaine self-administration decreases a-adrenoceptor regulation of mGluR-mediated inhibition in dopamine neurons. J. Neurosci. 2004 June; 24: 5209-5215 Paladini C. A., and Williams J. T.; Noradrenergic inhibition of midbrain dopamine neurons. J. Neurosci. 2004 May; 24: 4568-4575. Paladini C. A., Robinson S, Morikawa H, Williams J. T., Palmiter R.; Dopamine controls the firing pattern of dopamine neurons via a network feedback mechanism. PNAS. 2003 Mar; 100: 2866-2871. Tepper, J. M., Celada, P., Iribe, Y. and Paladini, C. A. (2002) Afferent Control of Nigral Dopaminergic Neurons: The Role of GABAergic Inputs. In Graybiel, A.M. and DeLong, M.R., eds. The Basal Ganglia VI, Kluwer Academic Publishers, Norwell. Paladini C. A., Fiorillo C. D., Morikawa H. and Williams J. T.; Amphetamine Selectively Blocks Inhibitory Glutamate Transmission in Dopamine Neurons. Nature Neurosci. 2001 Mar; 4(3): 275-281. |
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Neuroscience Links:
http://bio.utsa.edu/snrp/Home.html |
UTSA Specialized Neuroscience Research Programs |
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Carlos
A. Paladini, Ph.D.
