Rueben A. Gonzales, Ph.D.

Reuben Gonzalez Profile Pic

Professor of Pharmacology & Toxicology
Jacques P. Servier Regents Professor in Pharmacy

Content
Gonzales Lab Image Home Page collage - diagram, charts, lab equipment, microdialysis probe

Research Interests

The overall goal is to understand the neurochemical basis for ethanol drinking behavior. Since the brain controls behavior, and neurons are the basic functional unit of the brain, it follows that neuronal activity underlies ethanol drinking behavior. Neuronal activity is controlled in part by the chemical microenvironment, so a major objective of the lab is to characterize the chemical changes in the brain that may underlie alcohol drinking. The research entails a combination of behavioral and chemical techniques.

Current interests include the effects of ethanol on basic dopaminergic neuronal activity in vivo, and the involvement of dopamine in ethanol self-administration behavior. Other interests include the physical characterization and theoretical description of diffusion behavior of solutes during in vivo microdialysis. Two new projects have been undertaken in the lab in the last few years. We have begun development of microdialysis for opioid peptides. This new analytical technique will enable analysis of larger messenger molecules and their roles in ethanol-related behaviors.  Secondly, we are exploring new models of ethanol self-administration to better investigate the transition from controlled to uncontrolled ethanol self-administration.

Neuropharmacology

This graduate course (PGS 383D, cross listed with NEU 383D) surveys the major neurotransmitter systems which mediate the mechanism of action of drugs which act on the central nervous system. The focus of the course is on molecular mechanisms of drug action. Drugs used in the experimental analysis of pharmacological mechanisms will be discussed along with clinically used drugs. The course is team taught by the neuropharmacology faculty in the Division of Pharmacology. Dr. Laura Fonken coordinates the course. It is offered every spring. Prerequisite is Biomedical Pharmacology I or consent of instructor. A background in physiology and biochemistry is strongly recommended.

An example of the syllabus (PDF) is available. For further information contact Dr. Gonzales or Dr. Fonken.

 

Laboratory Problems in Pharmacology

Problems courses are available for graduate and undergraduate students interested in gaining first hand experience in neuropharmacological research. Refer to the information under each faculty member for specifics of the range of research problems which are currently being studied in the Division of Pharmacology and Toxicology.

Dr. Gonzales is currently offering Laboratory Problems courses in research pertaining to the neurochemical mechanisms of action of ethanol using the technique of microdialysis.

For further information contact Dr. Gonzales.

 

Microdialysis

These studies are investigating the mechanism of ethanol’s intoxicating effects using the method of microdialysis. With this method molecules in the extracellular fluid of the brain can be measured including neurotransmitters such as dopamine and excitatory amino acids. A microdialysis probe is placed in a defined brain region (striatum, nucleus accumbens, or hippocampus) and the dialysate is analyzed for levels of the neurotransmitters. Ethanol can be perfused through the microdialysis probe or administered i.p. Since the rat is conscious and freely moving during the drug treatment and microdialysis sampling, the drug-induced behavior can be correlated with changes in extracellular levels of neurotransmitters. By measuring both neurochemical and ethanol-induced changes we hope to gain evidence for the neurochemical basis of ethanol-induced behavior.

This area is currently the major focus of research in my lab.

For further information contact Dr. Gonzales.

 

Other Teaching Interests

The following publications are from a list of 79.

  1. Valenta JP, Gonzales RA.  Chronic intracerebroventricular infusion of monocyte chemoattractant protein – 1 leads to a persistent increase in sweetened ethanol consumption during operant self-administration but does not influence sucrose consumption in Long-Evans rats, Alcohol Clin Exp Res, 40:187-195, 2016.

  2. Barker JM, Corbit LH, Robinson DL, Gremel CM, Gonzales RA, Chandler LJ.  Corticostriatal circuitry and habitual alcohol seeking, Alcohol, in press.

  3. Doherty, J.M. and Gonzales, R.A.  Lack of effect of nucleus accumbens dopamine D1 receptor blockade on consumption during the first two days of operant self-administration of sweetened ethanol in adult Long-Evans rats, Alcohol, 49:543-51, 2015

  4. Reno, J., Thakore, N., Gonzales, R.A., Schallert, T., Ribell, Maddox, T., Duvauchelle, C.L.  Alcohol-preferring P rats emit spontaneous 22-28kHz ultrasonic vocalizations that are altered by acute and chronic alcohol experience, Alcohol Clin Exp Res, 39: 843-52, 2015

  5. Doherty, J.M. and Gonzales, R.A.  Operant self-administration of sweetened ethanol and time course of blood ethanol levels in adolescent and adult male Long-Evans rats, Alcohol Clin Exp Res, 39:485-95, 2015.

  6. Vena, A.A. and Gonzales, R.A.  Temporal Profiles Dissociate Regional Extracellular Ethanol versus Dopamine Concentrations, ACS Chem Neurosci 6: 37-47, 2015.

  7. Mangieri, R.A., Cofresí, R.U., Gonzales, R.A.  Ethanol exposure interacts with training conditions to influence behavioral adaptation to a negative instrumental contingency, Front Behav Neurosci. 8: 220. doi: 10.3389/fnbeh.2014.00220, 2014.

  8. Valenta, J.P., Job, M.O., Mangieri, R.M., Schier, C.J., Howard, E.C., Gonzales, R.A.  mu-Opioid receptors in the stimulation of  mesolimbic dopamine activity in Long-Evans rats  by ethanol and morphine: a delayed effect of ethanol, Psychopharmacology 228: 389-400, 2013.

  9. Schier, C.J., Dilly, G.A., Gonzales, R.A.  Intravenous Ethanol Increases Extracellular Dopamine in the Medial Prefrontal Cortex of the Long-Evans Rat, Alcohol Clin Exp Res 37: 740-7, 2013.

  10. Schier, C J., Mangieri, R.A., Dilly, G.A., Gonzales, R.A. Microdialysis of Ethanol During Operant Ethanol Self-administration and Ethanol Determination by Gas Chromatography. J. Vis. Exp. (67), e4142, DOI: 10.3791/4142 (2012).

  11. Mangieri, R.A., Cofresi, R.U. Gonzales, R.A.  Ethanol Seeking by Long Evans Rats Is Not Always a Goal-Directed Behavior PLoS ONE 7: e42886. doi:10.1371/journal.pone.0042886, 2012

  12. Carrillo, J. and Gonzales, R.A.  A single exposure to voluntary ethanol self-administration produces adaptations in ethanol consumption and accumbal dopamine signaling, Alcohol 45: 559-566, 2011.

  13. Ramachandra, V., Kang, F., Kim, Christine, Nova, A.S., Bajaj, A., Hall, F.S., Uhl, G.R., Gonzales, R.A.  The mu opioid receptor is not involved in ethanol-stimulated dopamine release in the ventral striatum of C57BL/6J mice, Alcohol Clin Exp Res 35: 1-10, 2011

  14. Theile, J.W., Morikawa, H., Gonzales, R.A., Morrisett, R.A.  GABAergic transmission modulates ethanol excitation of ventral tegmental area dopamine neurons, Neuroscience 172: 94-103, 2011

  15. Theile, J.W., Gonzales, R.A., Morrisett, R.A.  Ethanol modulation of GABAergic inhibition in midbrain dopamine neurons:  implications for the development of alcohol-seeking behaviors, in Inhibitory Synaptic Plasticity, MA Woodin, A. Maffei, eds., Springer, New York, pp 75-88, 2011.

  16. Howard, E.C., Schier, C.J., Wetzel, J.S., Gonzales, R.A.  The dopamine response in the nucleus accumbens core-shell border differs from that in the core and shell during operant ethanol self-administration, Alcohol Clin. Exp. Res. 33: 1355-1365, 2009.

  17. Theile, J.W., Morikawa, H., Gonzales, R.A., Morrisett, R.A. Role of 5-HT2c receptors in Ca2+-dependent ethanol potentiation of GABA release onto ventral tegmental area dopamine neurons, J. Pharmacol. Exp. Ther.,329: 625-33, 2009.

  18. Robinson, D.L., Howard, E.C., McConnell, S., Gonzales, R.A., Wightman, R.M. Disparity between tonic and phasic ethanol-induced dopamine increases in the nucleus accumbens of rats, Alcohol Clin. Exp. Res., in press.

  19. Howard, E.C., Schier, C.J., Wetzel, J.S., Duvauchelle, C.L., Gonzales, R.A. The shell of the nucleus accumbens has a higher dopamine response compared with the core after non-contingent intravenous ethanol administration, Neuroscience 154: 1042-1053, 2008.

  20. Theile, J., Morikawa, H., Gonzales, R.A., Morrisett, R.A. Ethanol enhances GABAergic transmission onto dopamine neurons in the ventral tegmental area of the rat, Alcohol Clin Exp Res. 32: 1040-1048, 2008.

  21. Carrillo, J., Howard, E.C., Moten, M., Houck, B.D., Czachowski, C.L., Gonzales, R.A. A three-day exposure to 10% ethanol with 10% sucrose successfully initiates ethanol self-administration, Alcohol 42: 171-178, 2008.

  22. Ramachandra, V., Phuc, S., Franco, A.C., Gonzales, R.A. Ethanol preference is inversely correlated with ethanol-induced dopamine release in two substrains of C57BL/6 mice, Alcohol Clin. Exp. Res. 31: 1669-76, 2007.

  23. Job, M.J., Tang, A., Hall, F.S., Sora, I., Uhl, G.R., Bergeson, S.E., Gonzales, R.A. Mu opioid receptor regulation of ethanol-induced dopamine response in the ventral striatum: evidence of genotype specific sexual dimorphic epistasis, Biol. Psychiatry, 62: 627-34, 2007.

  24. Zapata, A., Gonzales, R.A., Shippenberg, T.S. Repeated ethanol intoxication induces behavioral sensitization in the absence of a sensitized accumbens dopamine response in C57BL/6J and DBA/2J mice. Neuropsychopharmacology 31:396-405, 2006

Gonzales Lab Photo - Probe

 

Photomicrograph of a microdialysis probe. Probes are constructed in the lab. The tubing in the middle is fused silica tubing with an inner diameter of 40 microns. This delivers the perfusate to the probe tip. The membrane is cellulose. The perfusate flows out of the inner tubing and is contained within the membrane. The exit port (not shown) is another piece of fused silica tubing.

Contact Information
Phone:
512-471-5192
Campus location:
PHR 5.224C

US Mail Address:
The University of Texas at Austin
PHR 5.224C
2409 University Ave., A1915
Austin, TX 78712

FEDEX Address:
107 W. Dean Keeton St.
PHR 5.224C
The University of Texas at Austin
Austin, TX 78712