About

Reuben A. Gonzales, Ph.D., is a Professor Emeritus of Pharmacology & Toxicology and a Jacques P. Servier Regents Professor Emeritus at the University of Texas at Austin. His research focuses on understanding the neurochemical basis for ethanol drinking behavior, emphasizing the role of neuronal activity controlled by the brain's chemical microenvironment. His laboratory employs behavioral and chemical techniques to investigate how ethanol affects dopaminergic neuronal activity in vivo and the involvement of dopamine in ethanol self-administration behavior. Current projects include developing microdialysis techniques for opioid peptides and exploring models of ethanol self-administration to better understand the transition from controlled to uncontrolled alcohol consumption. Dr. Gonzales also teaches graduate courses in neuropharmacology, covering neurotransmitter systems and the molecular mechanisms of drug action, and offers research opportunities through laboratory problems courses related to neurochemical mechanisms of ethanol action. His extensive research has contributed to the understanding of ethanol's effects on neurotransmitter systems, including dopamine and GABA, and their roles in alcohol-seeking behaviors. His work involves advanced techniques such as microdialysis to measure extracellular neurotransmitter levels in the brain, providing insights into the neurochemical underpinnings of alcohol intoxication and addiction.

Research topics

• Endocrinology
• Biochemistry
• Neuroscience
• Internal medicine
• Chemistry
• Medicine
• Psychology
• Biology
• Clinical psychology
• Pharmacology

Selected publications

• Neuron-specific modulation of SLC30A10 identifies dopaminergic and glutamatergic neurons as targets of manganese-induced motor disease

  Proceedings of the National Academy of Sciences · 2026-02-02

  articleOpen access

  Essential metals accumulate in the basal ganglia at elevated levels and induce incurable motor disease. But, unlike other motor diseases, the neuronal targets of essential metals are unknown, and this fundamental knowledge gap has limited therapeutic progress. Because metal efflux transporters have high specificity, we hypothesized that neuron-specific knockout or knockin (i.e., overexpression) of efflux transporters may alter metal levels in targeted neurons and define the neuronal targets of metal-induced disease. To test this, we focused on manganese (Mn)-induced motor disease, which is a public health problem. We generated six neuron-specific Slc30a10 mouse strains with knockout or knockin of the Mn efflux transporter Slc30a10 in dopaminergic, GABAergic, or glutamatergic neurons. In the knockout strains, SLC30A10 was depleted and Mn levels were elevated in targeted brain regions. However, only dopaminergic- or glutamatergic-, but not GABAergic-, specific knockouts developed motor deficits without Mn exposure. Conversely, in the knockins, SLC30A10 was elevated and the increase in Mn levels after Mn exposure was attenuated in targeted regions. However, only dopaminergic- or glutamatergic-, but not GABAergic-, specific knockins were protected against Mn-induced motor deficits. Dopaminergic-specific Slc30a10 knockouts also exhibited deficits in dopaminergic neurotransmission that were consistent with their motor phenotype. Overall, 1) elevated Mn targets dopaminergic and glutamatergic neurons to induce motor disease, and 2) neuron-specific knockout/knockin of efflux transporters is an effective strategy to isolate the neuronal targets and underlying mechanisms of metal-induced neurological disease.

  PublisherDOI

• CO ₂ Reactivity but Not CO ₂ ‐Induced Orexin/c‐Fos Colocalization Differentially Predicts Alcohol‐Seeking Behaviour After Extinction and Retrieval‐Extinction in Rats

  Addiction Biology · 2026-01-01

  articleOpen access

  ABSTRACT Cues associated with alcohol consumption can trigger cravings, seeking behaviour and relapse after abstinence in individuals with alcohol use disorder (AUD). These conditioned responses can be attenuated through extinction learning, a core component of cue exposure therapy (CET). CET is effective in some individuals with AUD but not all, so it is necessary to develop strategies to identify and intervene with individuals unlikely to benefit from CET. Another method for attenuating conditioned responding is retrieval‐extinction, which renders the original associative memory labile via distinct neural mechanisms. We recently demonstrated that CO 2 reactivity predicts extinction memory for both fear and food cues, and fear memory after retrieval‐extinction, and CO 2 ‐induced orexin/c‐Fos colocalization predicts fear extinction memory. The purpose of the current study was to examine whether the predictive power of CO 2 reactivity might extend to alcohol‐seeking behaviour after extinction or retrieval‐extinction in male and female rats. We also examined the relationship between CO 2 reactivity, return of alcohol‐seeking behaviour and CO 2 ‐induced orexin/c‐Fos colocalization. Male and female rats first underwent alcohol drinking induction in the homecage followed by dependence via exposure to chronic intermittent ethanol vapour or control air and homecage drinking. All rats then underwent Pavlovian alcohol conditioning followed by either standard extinction or retrieval‐extinction. They then received a long‐term memory (LTM) test and CO 2 challenge followed by euthanasia for brain harvesting. CO 2 reactivity differentially predicted LTM after extinction and retrieval‐extinction. There were no relationships between orexin/c‐Fos colocalization and CO 2 reactivity or LTM. The predictive power of CO 2 reactivity extends to alcohol‐seeking behaviour after extinction and retrieval‐extinction in alcohol dependent and nondependent male and female rats, while its relationship with orexin/c‐Fos colocalization does not. CO 2 reactivity could be used as a screening tool to determine whether an individual may be a good candidate for CET or a retrieval‐extinction–based approach.

  PublisherDOI

• Context‐Dependent Extinction and Return of Pavlovian Alcohol‐Seeking Behavior in Male and Female Rats

  Alcohol Clinical and Experimental Research · 2026-04-01

  articleOpen access

  BACKGROUND: Environmental cues can become conditioned stimuli when associated with alcohol consumption, facilitating alcohol-seeking behavior and increasing relapse risk. Extinguishing alcohol-seeking behavior may reduce cue-induced responses; however, conditioned responding often occurs when the cue is presented in a different context than the one where the behavior was extinguished. Although prior research suggests that males generally show stronger context-dependent return of conditioned appetitive and fear responses, it is not known whether this sex difference extends to conditioned responses to alcohol-associated cues. METHODS: After a 5-week alcohol induction period, adult male and female Long-Evans rats underwent Pavlovian conditioning in Context A, where a 15% unsweetened alcohol solution was paired with a light cue. Extinction sessions were conducted in a distinct Context B in the absence of alcohol, followed by a test session in Context B (LTM) and then in Context A. RESULTS: Both sexes successfully extinguished alcohol-seeking behavior in Context B but exhibited robust alcohol-seeking behavior when reintroduced to the alcohol-associated context, Context A. No significant sex differences were observed in the magnitude of reemerged conditioned responding. CONCLUSIONS: These findings suggest that changes of context induce alcohol-seeking behavior to return similarly in male and female rats, indicating that sex-independent mechanisms may underlie contextual relapse processes.

  PublisherOA PDFDOI

• Corrigendum to “Time-course concentration of ethanol, acetaldehyde and acetate in rat brain dialysate following alcohol self-administration” [Alcohol 123 (2025) 69–76]

  Alcohol · 2025-04-23

  erratumOpen access
  PublisherDOI

• Correction to: Acute phenylalanine/tyrosine depletion of phasic dopamine in the rat brain

  UNC Libraries · 2025-09-09

  articleOpen access
  PublisherDOI

• Experimental investigation of regenerated cellulose microdialysis probe sterilization

  Journal of Applied Polymer Science · 2024-03-06 · 1 citations

  articleOpen access

  Sterilization of devices is important in hospitals, operating theatres, and emergency rooms. Microdialysis allows in vivo sampling of small molecules and is used for clinical studies. Microdialysis probes are made of soft, flexible, porous polymeric membranes. They have been traditionally disinfected using either ethanol (which fails to eliminate all microbes and doesn't satisfy regulatory requirements) or ethylene oxide gas and gamma irradiation (that are expensive and resource-intensive). In this work, three methods for microdialysis probe-sterilization were studied - autoclave and two chemicals (commercially available sterilization solutions): Sporox II and MetriCide. Following sterilization, the regenerated cellulose membranes were characterized under scanning electron microscopy and by measuring the changes in pore characteristics using nitrogen sorption. To determine the effect of sterilization on analyte diffusion through the membrane, microdialysis probes were fabricated, sterilized and tested with two analytes; ethanol and dopamine. The autoclaved membranes suffered thermo-mechanical damage and were deemed unfit for further testing. Probes sterilized with the chemical solutions were subsequently characterized by in vitro microdialysis experiments performed under regulated mass flux conditions. It is concluded that autoclaving is not a suitable sterilization technique for the cellulose membranes, while both of the chemical sterilizers were found to be good candidates for sterilization.

  PublisherOA PDFDOI

• MEN OF MEXICAN ETHNICITY, ALCOHOL USE, AND HELP-SEEKING: “I CAN QUIT ON MY OWN.”

  Drug and Alcohol Dependence · 2024-08-01

  article
  PublisherDOI

• Experimental and numerical investigation of microdialysis probes for ethanol metabolism studies

  Analytical Methods · 2024-01-01 · 4 citations

  articleOpen access

  experimental results with numerical simulations enabled us to calculate diffusion coefficients of molecules in the microdialysis membranes and study the extent of the depletion effect caused by continuous microdialysis sampling, thus providing additional insights for probe selection and data interpretation.

  PublisherOA PDFDOI

• Time-course concentration of ethanol, acetaldehyde and acetate in rat brain dialysate following alcohol self-administration

  Alcohol · 2024-09-06 · 1 citations

  articleOpen access

  The unclear mechanisms of ethanol metabolism in the brain highlight the need for a deeper understanding of its metabolic pathways. This study used in vivo microdialysis to simultaneously sample ethanol and its metabolites, acetaldehyde and acetate, in the rat striatum following self-administration of ethanol, emphasizing the natural oral exposure route. To enhance the self-administration, rats underwent two-bottle-choice and limited access training. Dialysate samples, collected every 10 min for 2.5 h, were analyzed using gas chromatography with flame ionization detection (GC-FID). The measured time courses of dialysate concentrations of ethanol, acetaldehyde, and acetate provided insights into dynamics of ethanol metabolism. Notably, in a subject with low ethanol consumption (0.29 g/kg), the concentration of acetaldehyde remained below the limit of detection throughout the experiment. However, the acetate concentration was clearly increased after ethanol consumption in this subject and was comparable to that of other rats with higher ethanol consumption. Compared with focusing only on peak values in the time-courses of concentrations of ethanol and its metabolites, calculating areas under curves provided better models of the relationships between ethanol intake and individual ethanol metabolites, as indicated by the R-square values for the linear regressions. This approach of using the area under the curve accounts for both the amplitude and duration of the concentration profiles, reducing the impact of variations in individual drinking patterns. In vivo microdialysis enables concurrent sampling of brain metabolites during oral ethanol administration, contributing insights into metabolite dynamics. To our knowledge, this paper is the first to report measurement of all three analytes in the brain following self-administration of ethanol. Future studies will explore regional variations and dynamics post-ethanol dependence, further advancing our understanding of ethanol metabolism in the brain.

  PublisherDOI

• SLC30A10 manganese transporter in the brain protects against deficits in motor function and dopaminergic neurotransmission under physiological conditions

  Metallomics · 2023 · 21 citations

  • Chemistry
  • Neuroscience
  • Internal medicine

  Loss-of-function mutations in SLC30A10 induce hereditary manganese (Mn)-induced neuromotor disease in humans. We previously identified SLC30A10 to be a critical Mn efflux transporter that controls physiological brain Mn levels by mediating hepatic and intestinal Mn excretion in adolescence/adulthood. Our studies also revealed that in adulthood, SLC30A10 in the brain regulates brain Mn levels when Mn excretion capacity is overwhelmed (e.g. after Mn exposure). But, the functional role of brain SLC30A10 under physiological conditions is unknown. We hypothesized that, under physiological conditions, brain SLC30A10 may modulate brain Mn levels and Mn neurotoxicity in early postnatal life because body Mn excretion capacity is reduced in this developmental stage. We discovered that Mn levels of pan-neuronal/glial Slc30a10 knockout mice were elevated in specific brain regions (thalamus) during specific stages of early postnatal development (postnatal day 21), but not in adulthood. Furthermore, adolescent or adult pan-neuronal/glial Slc30a10 knockouts exhibited neuromotor deficits. The neuromotor dysfunction of adult pan-neuronal/glial Slc30a10 knockouts was associated with a profound reduction in evoked striatal dopamine release without dopaminergic neurodegeneration or changes in striatal tissue dopamine levels. Put together, our results identify a critical physiological function of brain SLC30A10-SLC30A10 in the brain regulates Mn levels in specific brain regions and periods of early postnatal life, which protects against lasting deficits in neuromotor function and dopaminergic neurotransmission. These findings further suggest that a deficit in dopamine release may be a likely cause of early-life Mn-induced motor disease.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R23AA007297

  NIH · $155k · 1990

• NIH Grant R01AA011852

  NIH · $1.9M · 2009

• NIH Grant R01AA014874

  NIH · $2.7M · 2019

• NIH Grant R37AA011852

  NIH · $2.8M · 2020

• Neurochemical & Behavioral Correlates of ETOH Effects

  NIH · $10.7M · 1987–2027

Frequent coauthors

• Fulton T. Crews

  26 shared

• Roberto U. Cofresí

  University of Missouri

  15 shared

• Hyeon Joo Yim

  14 shared

• Richard L. Bell

  Agricultural Research Service

  14 shared

• William M. Doyon

  University of Pennsylvania

  14 shared

• Vorani Ramachandra

  The University of Texas at Austin

  13 shared

• Cristine L. Czachowski

  University of Indianapolis

  13 shared

• Peter M. Bungay

  University Hospitals of Derby and Burton NHS Foundation Trust

  13 shared

Awards & honors

• Jacques P. Servier Regents Professor Emeritus