Linda Dwoskin - Ph.D.
Dr. Dwoskin is an Endowed Professor in Pharmaceutical Education at the University of Kentucky College of Pharmacy. She also is Director and Principal Investigator of a National Cooperative Drug Discovery Group (NCDDG) which collaborates with the National Institutes of Health (NIH) to discover novel treatments for tobacco smoking cessation. She received her B.S. (1974) in psychology from Syracuse University, and Ph.D. (1983) from the Department of Pharmacology at the University of Minnesota. She was a postdoctoral fellow in endocrinology at the Oregon Health Science Center and in the Department of Pharmacology at the University of Colorado Health Science Center. Dr. Dwoskin joined the faculty at the University of Kentucky in 1988 as an assistant professor. She currently holds several other academic appointments including: professor, Department of Behavioral Sciences; adjunct faculty, University of Kentucky Graduate Center; associate, University of Kentucky Center on Drug Abuse Translation; associate, Multi-disciplinary Research Center on Drug and Alcohol Abuse; and associate, Center of Membrane Sciences. Dr. Dwoskin has been awarded the University of Kentucky Wethington Award for Meritorious Performance in Research (2002-2006). She was chosen in 2005-2006 for a University Research Professorship, recognizing her outstanding research and her distinguished record of achievement in her field. Her research has resulted in over 145 peer-reviewed research articles, 250 abstracts of research presentations and 49 patents and patent applications. Dr. Dwoskin's major research focus is drug discovery in neuropharmacology, i.e., the development of novel therapeutic candidates for the treatment of psychostimulant abuse, specifically for nicotine and methamphetamine abuse. In particular, her focus is the design and discovery of subtype-selective neuronal nicotinic receptor antagonists as novel tobacco smoking cessation agents and of modulators of vesicular monoamine transporter function as novel treatments for methamphetamine abuse. In her collaborators labs, promising therapeutic candidates are also tested in locomotor activity assays and drug discrimination assays to determine if they inhibit the stimulant effects and interoceptive cues associated with psychostimulant use, as well as in intravenous self-administration assays to determine if they inhibit the rewarding effect of these drugs of abuse. Another focus of Dr. Dwoskin's research is to determine the role of environmental and genetic factors as determinants of individual responsiveness to drugs of abuse and as determinants of an individual's potential for abuse liability. Using an animal model, the relationship between dopaminergic function (release, reuptake and metabolism) in striatum, nucleus accumbens, medial prefrontal cortex and orbital prefrontal cortex and an individual's behavior in novelty-seeking, psychostimulant self-administration and delay-discounting assays are evaluated as predictors of an individual's responsiveness to drugs of abuse. Several drugs discovered in her laboratory at the University of Kentucky are currently in various phases of clinical development. Dr. Dwoskin has graduated 3 Ph.D. students and 1 Masters student and has 4 graduate students in her laboratory currently. She has trained 17 postdoctoral fellows in her laboratory.Dr. Dwoskin's CV [MS WORD].
- Wilkins L.H., Miller D.K., Crooks P.A. and Dwoskin L.P. N-n-Alkylnicotinium analogs, a novel class of antagonists at Î±4Î²2* nicotinic acetylcholine receptors: Inhibition of S(-)-nicotine-evoked 86Rb+ efflux from rat thalamic synaptosomes. AAPS Journal: AAPS-NIDA Symposium, Frontiers in Science: Drug Addiction: From Basic Research to Therapeutics, AAPS Journal 7:E922-930, 2006.
- Sumithran S.P., Crooks P.A., Xu R., Zhu J., Deaciuc A.C., Wilkins L.H. and Dwoskin L.P. Incorporation of unsaturation into the N-n-alkyl chain of the nicotinic receptor antagonists, NONI and NDNI: Effect on affinity and selectivity. AAPS Journal, 7:E201-E217, 2005.
- Zhu J., Apparsundaram S., Bardo M.T., Dwoskin L.P. Environmental enrichment decreases cell surface expression of the dopamine transporter in rat medial prefrontal cortex. J. Neurochem., 93:1434-1443, 2005. Neugebauer, N. S., Zhang, Z., Crooks, P. A., Dwoskin, L. P. and Bardo, M. T. Effect of a novel nicotinic receptor antagonist, N,Nâ€™-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB), on nicotine self-administration and hyperactivity in rats. Â Psychopharmacology 184:426-434, 2006.
- Wooter T.E., Dwoskin L.P. and Bardo M.T. Age and sex differences in the locomotor effects of repeated methylphenidate in rats classified as high or low responders. Psychopharmacology 188:18-27, 2006. Zheng G., Dwoskin L.P. and Crooks P.A. Vesicular monoamine transporter 2: Role as a novel target for drug development. AAPS Journal, NIDA -AAPS Symposium on Drugs of Abuse: Mechanisms of Toxicity, Toxicokinetics and Medical Consequences of Drugs of Abuse", 8(4), E682-E692, 2006.
- Dwoskin L.P., Rauhut A.S., King-Pospisil K.A. and Bardo M.T. Review of the pharmacology and clinical profile of bupropion, an antidepressant and tobacco use cessation agent. CNS Drug Reviews, 12(3-4):178-207, 2006.
- Huang X., Chen X., Zheng F., Crooks P.A., Dwoskin L.P. and Zhan C.-G. Modeling subtype-selective agonists binding with Î±4ÃŸ2 and Î±7 nicotinic acetylcholine receptors: Effects of local binding and lon-range electrostatic interactions. J. Med. Chem. 49:7661-7674, 2006.
- Middleton LS, Crooks PA, Wedlund PJ, Cass WA and Dwoskin L.P. Nornicotine inhibition of dopamine transporter function in striatum via nicotinic receptor activation. Synapse 61:157-165, 2007.
- Middleton LS, Apparsundaram S, King-Pospisil KA and Dwoskin L.P. Nicotine increases dopamine transporter function in rat striatum through a trafficking-independent mechanism. Eur J Pharmacol 554:128-136, 2007.
- Stairs D.J., Neugebauer N., Wei X., Cassis L., Crooks P.A., Dwoskin L.P. and Bardo M.T. In vivo pharmacology of nornicotine enantiomers: Effects on intravenous S(-) nicotine self-administration and cardiovascular function in rats. Psychopharmacology, 190:145-155, 2007.
- Rahman S., Neugebauer N.M., Zhang Z., Crooks P.A., Dwoskin L.P.and Bardo M.T. The effects of a novel nicotinic receptor antagonist, N,N-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB) on acute and repeated nicotine-induced increases in extracellular dopamine in rat nucleus accumbens. Neuropharmacology, 52:755-763, 2007.
- Zheng F., Zheng G., Deaciuc A.G., Zhan C.G., Dwoskin L.P. and Crooks P.A. Computational neural network analysis of the affinity of lobeline and tetrabenazine analogs for the vesicular monoamine transporter -2. Bioorg Med Chem. 15:2975-2992, 2007.
- Papke RL, Dwoskin L.P. and Crooks PA. The pharmacological fingerprint of nAChRs subtypes utilizing nicotine and nornicotine: Relevance to nicotine dependence and drug discovery. J Neurochem 101:160-167, 2007.
- Neugebauer N.M., Harrod S.B., Stairs D.J., Crooks P.A., Dwoskin L.P. and Bardo M.T. Lobelane decreases methamphetamine self-administration in rats. Eur. J. Pharmacol. 571:33-38, 2007.
- Zhu J, Bardo MT, Bruntz RC, Stairs DJ and Dwoskin L.P. Individual differences in response to novelty predict prefrontal cortex dopamine transporter function and cell surface expression. Eur J Neurosci 26:717-728, 2007
- Zhu J., Bardo M.T., Green T.A., Wedlund P.J. and Dwoskin L.P. Nicotine increases dopamine clearance in medial prefrontal cortex in rats raised in an enriched environment. J. Neurochem., Epub ahead of print, 2007.
- Dwoskin L.P., Joyce B.M., Zheng G., Neugebauer N.M., Manda V.K., Lockman P., Papke R.L., Bardo M.T. and Crooks P.A. Discovery of a novel nicotinic receptor antagonist for the treatment of nicotine addiction: 1(-3-Picolinium)-12-triethylammonium-dodcane dibromide (TMPD). Biochem Pharmacol 74:1271-1282, 2007.
- Norrholm S.D., Horton D.B. and Dwoskin L.P. The promiscuity of the dopamine transporter: Implications for the kinetic analysis of [3H]serotonin uptake in rat hippocampal and striatal synaptosomes. Neuropharmacology, 53:982-989, 2007.
- Zheng G., Zhang Z., Pivarvarchyk M., Deaciuc A.G., Dwoskin L.P. and Crooks P.A. bis-Azaaromatic quaternary ammonium salts as antagonists at nicotinic receptors mediating nicotine-evoked dopamine release: An investigation of binding conformation. Bioorg. Med. Chem. Let., 17:6734-6738, 2007.
- Zheng G., Sumithran S.P., Deaciuc A.G., Dwoskin L.P. and Crooks P.A. tris-Azaaromatic quaternary ammonium salts: Novel templates as antagonists at nicotinic receptors mediating nicotine-evoked dopamine release. Bioorg. Med. Chem. Let., 17:6701-6706, 2007.
- Kantak K.M., Singh T., Kerstetter K.A., Dembro K.A., Mutebi M.M., Harvey R.C., Deschepper C. F. and Dwoskin L.P. Advancing the spontaneous hypertensive rat model of attention deficit hyperactivity disorder. Behav. Neuroscience, in press, 2007.
- Lockman P.R., Manda V.K., Geldenhuys W.J., Mittapalli R.K., Thomas F., Albayati Z.F., Crooks P.A., Dwoskin L.P. and Allen D.D. Carrier-mediated transport at of the quaternary ammonium neuronal nicotinic receptor antagonist, N,Nâ€™-dodecyl-bis-picolinium dibromide (bPiDDB) at the blood-brain barrier. J. Pharmacol. Exp. Ther., 324:244-250, 2008