ADDICTION SCIENCE EDUCATION. For the last several years Carl Erickson and I have conducted workshops on the neurobiology of addiction around the country. We evaluate these workshops for effectiveness in changing knowledge, beliefs and professional behavior concerning the addictions. This work, consistently funded by NIAAA / NIDA, has resulted in a number of peer reviewed papers (both reviews and data papers). I plan to continue these activities for the foreseeable future.

MEDICAL OUTCOMES RESEARCH. A huge and growing percentage of the population of the Northwest Austin area consists of working poor families without health insurance. These individuals need education about diseases and preventative medicine. Free clinics, such as the one I work with, need models to evaluate their effectiveness in delivering all types of services. To this end I have developed and enhanced contacts throughout the community and at UT to provide a unique partnership for better health care for underserved people.

COMPUTATIONAL CHEMISTRY. My previous work in this area evaluated the structural features of agonists at dopamine D1 receptors D1 vs. D2 receptors, D2 wild type and mutant receptors, and 5HT7 receptors vs. dopamine receptors.

Key results in this area have demonstrated an increase in accuracy and precision of agonist affinity measurements when data from recombinant receptors stably expressed in cell lines are used. Also, these results have shown important similarities and differences in the structural requirements for agonist affinity at closely related receptors (receptor subtypes and wild type vs. point mutant variants).

This computational work extends 30 years of wet lab studies ranging from behavior through studies conducted in clonal cell lines on dopamine functions.

SUMMARY

During the past several years my research has embraced four major content / methods areas: computational chemistry models of drug - receptor interactions, quantitative models of drug action, signal transduction following in vivo drug challenge, and educational research in addiction.
a) Computational chemistry. See above.
b) Quantitative modeling. This set of papers determined agonist affinity and relative intrinsic efficacy at D1 and D2 dopamine receptors stably expressed in clonal cell lines in terms of cAMP production. Key results in this area have demonstrated an improved ability to determine agonist efficacy when studies of second messenger function are used in clonal cell lines stably expressing the receptor. Also, these results have shown that such expression systems represent useful model systems for testing pharmacological null hypotheses about the nature of drug receptor interactions. Finally, our results in this area have compared theoretical models for agonist.
c) Signal transduction. This set of papers evaluated the effects of dopaminergic agonists and antagonists vs. non-dopaminergic drugs on protein phosphorylation in corpus striatum following acute in vivo drug challenge. Key findings from these papers are that acute in vivo \drug challenge represents an important model for understanding protein phosphorylation in intact organisms. Furthermore, we have shown that both dopaminergic and non-dopaminergic drugs induce distinct patterns of protein phosphorylation (pDARPP-32 vs. pNR1) that are in some instances reversed by in vivo challenge with ethanol.
d) Addiction science education. See above.

AREAS OF EXPERTISE
Neuropharmacology / neurochemistry
Synaptic transmission / signal transduction
Parkinson's disease
Schizophrenia
Major depressive disorder
Bipolar disorder
Alzheimer's disease
Epilepsy
Attention deficit hyperactivity disorder
Anxiety

Recent Publications

• Brusniak, M. Y., R. S. Pearlman, et al. (1996). "Comparative molecular field analysis-based prediction of drug affinities at recombinant D1A dopamine receptors." Journal of Medicinal Chemistry 39(4): 850-9.

• Mak, C. K., M. Avalos, et al. (1996). "Improved models for pharmacological null experiments: calculation of drug efficacy at recombinant D1A dopamine receptors stably expressed in clonal cell lines." Neuropharmacology 35(5): 549-70.

• Erickson, C. K., R. E. Wilcox, et al. (1998). "Education of nonscientists about new alcohol research: results of two types of presentations plus 6-month follow-up." Alcoholism: Clinical & Experimental Research 22(9): 1890-7.

• Wilcox, R. and B. McMillen (1998). "The rational use of drugs as therapeutic agents for the treatment of the alcoholisms." Alcohol. 15(2): 161-77.

• Wilcox, R., T. Tseng, et al. (1998). "CoMFA-based prediction of agonist affinities at recombinant D1 vs. D2 dopamine receptors." J. Med. Chem. 41: 4385-4399.

• Wilcox, R. E., R. A. Gonzales, et al. (1998). Introduction to neurotransmitters, receptors, signal transduction and second messengers. Textbook of Psychopharmacology. C. B. Nemeroff and A. F. Schatzberg, American Psychiatric Press: 3-36.

• Avalos, M. A., C. Mak, et al. (2000). "Non-linear analysis of partial dopamine agonist effects on camp in c6 glioma cells." J. Pharm. Tox. Meth. 45: 17-37.

• Edwards, S., S. L. Hoyler, et al. (2000). "Beta2-adrenoreceptor inverse agonists enhance cAMP accumulation via up-regulation of functional receptor density at the cell surface." Soc. Neuroscience Abstr 26: 116 (45.14).

• Galindo, D., S. Edwards, et al. (2000). "Comparative effects of a full D1 agonist, a D2 receptor agonist, and ethanol on the phosphorylation of DARPP-32 and the NR1 subunit of the NMDA receptor." Society for Neuroscience Abstracts 30: 786 (#290.6).

• Raofi, S., P. K. Wong, et al. (2000). "Modulation of G-protein linked cAMP accumulation in immortalized murine cortical astrocytes by retroviral infection." Brain Research 862(1-2): 230-3.

• Wilcox, R. E. (2000). Dopamine. Encyclopedia of Psychology and Neuroscience, 3rd edition. W. E. Craighead and C. B. Nemeroff. New York, John Wiley. 1: 454-457.

• Wilcox, R. E. and C. K. Erickson (2000). "Commentary - Neurobiological aspects of the addictions." J. Addictions Nursing, 12(3/4), 117-133 12(3/4): 117-133.

• Wilcox, R. E., W.-H. Huang, et al. (2000). "CoMFA-based prediction of agonist affinities at recombinant wild type versus serine to alanine point mutated D2 dopamine receptors." Journal of Medicinal Chemistry 43(16): 3005-3019.

• Wilcox, R. E., J. E. Ragan, et al. (2000). "High-affinity agonist interactions at recombinant 5HT7 receptors - estimates using CoMFA (comparative molecular field analysis)." Soc. Neuroscience Abstr. 26: 2157 (810.9).

• Chu, J., W. Wilczynski, et al. (2001). " Pharmacological Characterization of the D1 and D2-like Dopamine Receptors from the Brain of the Leopard Frog, Rana pipiens." Brain Behavior and Evolution 57: 328-342.

• Doherty, J. M. and R. E. Wilcox (2001). "Acute in vivo dopaminergic drug effects on striatal versus nucleus accumbens protein phosphorylation." Bain Research: in progress.

• Erickson, C. K. and R. E. Wilcox (2001). "Pharmacology of addiction." Tex. Pharm. Assoc. J. winter: 8-13.

• Erickson, C. K. and R. E. Wilcox (2001). "Neurobiological causes of addictions." J. Social Work Practice in the Addictions 1(3): 7-22.

• Wilcox, R. E. and C. K. Erickson (2001). Brain biology of drug abuse and addiction. Neurobiology of Addictions - Implications for Clinical Practice. R. T. Spence, D. M. DiNitto and S. L. A. Straussner. Binghamton, NY, Haworth Press, Inc.: 7-23.

• Wilcox, R. E., J. E. Ragan, et al. (2001). "High-affinity interactions of ligands at recombinant guinea pig 5HT7 receptors." J. Computer-Aided Molecular Design 15: 883-909.

• Edwards, S., S. L. Hoyler, et al. (2002). "Sensitization of beta2-adrenoreceptor-mediated cAMP generation after chronic exposure to inverse agonists." British J. Pharmacology: in preparation.

• Edwards, S., D. Simmons, et al. (2002). "Antagonistic Effects of Dopaminergic Signaling and Ethanol on PKA-Mediated Phosphorylation of DARPP-32 and the NR1 Subunit of the NMDA Receptor." Alcoholism: Clinical and Experimental Research 26(2): 173-180.

• Huang, W.-H., R. E. Wilcox, et al. (2002). "Comparative Molecular Field Analysis (CoMFA) for sulfoxidation reactions in Mortierella isabellina ATCC 42613 and Helminthosporim sp. NRRL 4671." J. Molecular Modeling 8: 8-23.

• Scott, A., J. Doherty, et al. (2002). "Oxotremorine-M, oxotremorine-S, and eticlopride/naltrexone, but not fluoxetine, enhance striatal phosphorylation of the NMDA-R1 receptor subunit in mice following acute in vivo challenge." Brain Research: in preparation.

• Trzeciakowskii, J. P. and R. E. Wilcox (2002). "Estimating the relative efficacy of partial dopamine receptor agonists in recombinant receptor expression systems: Comparison of functional interaction and combined effects models." J. Thoretical Biol.: submitted.

• Doddakashi, V., L. Hauser, et al. (2003). "Female suicide in Texas 1994 -1998." Texas Medicine: in press.

• Erickson, C. K., R. E. Wilcox, et al. (2003). "Effectiveness of Addiction Science Presentations to Treatment Professionals, Using a Modified Solomon Study Design." Journal of Drug Education in press.

• Lawson, K. A., R. E. Wilcox, et al. (2003). "Educating Professionals to Promote Addiction Science Research: Demographics of Knowledge and Belief Changes." Substance Abuse and Misuse 2003.

• Li, S., D. Simmons, et al. (2003). "Acute in vivo challenge with the antidepressant fluoxetine enhances expression of striatal pDARPP-32, an effect that is reversed by ethanol." J. Neural Trans.: in preparation.

• Wilcox, R. E. and C. K. Erickson (2003). "Prevention of relapse to addiction - information for the practitioner." Texas Medicine submitted.

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21 June 2007 Faculty Directory College of Pharmacy at UT Austin Comments to: pharmacy@www.utexas.edu