Sergio Dominguez Lopez, Ph.D.
Research Assistant Member
Aging & Metabolism Research Program
Research
Our research goal is to understand how abused drugs alter brain circuitry to develop addictive behavior. The neurotransmitter dopamine is essential to abused drugs' addictive properties and the persistent motivation for drug-seeking. However, chronic exposure to highly addictive drugs such as methamphetamine also produced neurodegeneration of dopamine circuitry. Our preliminary data indicate that this derives from increased oxidative stress with chronic methamphetamine exposure.
In our experiments, we apply new technology for genetic fluorescence tagging of active neuronal populations and single-cell genetics. This approach allows us to determine the molecular profile of dopamine neurons than can be resistant or vulnerable to methamphetamine-induced oxidative stress. In addition, we are tracking the progressive changes in mitochondrial oxidative function, axonal degeneration, and dopamine neuron survival, to understand the time course and severity of metabolic and cellular damage occurring in these identified neurons. In summary, our research aims to identify the anatomical location, the metabolic and genetic traits of dopamine circuits encoding addictive behaviors.
In the long-term, using this cell to system approach, our research will contribute valuable knowledge to identify molecular targets to develop next-generation therapeutics to offer a healthier life quality for those fighting drug addictions.
Publications
Recent Publications
Howell RD, Dominguez-Lopez S, Ocañas SR, Freeman WM, Beckstead MJ. Female mice are resilient to age-related decline of substantia nigra dopamine neuron firing parameters. Neurobiol Aging 95:195-204, 2020 August, PMID: 32846275, PMCID: PMC7606778
Dominguez-Lopez S, Sharma R, Beckstead MJ. Neurotensin receptor 1 deletion decreases methamphetamine self-administration and the associated reduction in dopamine cell firing. Addict Biol:e12854, 2019 November, PMID: 31742874
Dominguez-Lopez S, Piccart E, Lynch WB, Wollet MB, Sharpe AL, Beckstead MJ. Antagonism of Neurotensin Receptors in the Ventral Tegmental Area Decreases Methamphetamine Self-Administration and Methamphetamine Seeking in Mice. Int J Neuropsychopharmacol 21:361-370, 2018 April, PMID: 29272412, PMCID: PMC5888879
Dominguez-Lopez S, Sharma R, Beckstead MJ. Neurotensin receptor 1 deletion decreases methamphetamine self-administration and the associated reduction in dopamine cell firing. Addict Biol:e12854, 2019 November, PMID: 31742874, PMCID: PMC8011996 (available on 2022-01-01)
Dominguez-Lopez S, Piccart E, Lynch WB, Wollet MB, Sharpe AL, Beckstead MJ. Antagonism of Neurotensin Receptors in the Ventral Tegmental Area Decreases Methamphetamine Self-Administration and Methamphetamine Seeking in Mice. Int J Neuropsychopharmacol 2018 Apr 1;21(4):361-370. PMID: 29272412, PMCID: PMC5888879
McCall NM, Kotecki L, Dominguez-Lopez S, Marron Fernandez de Velasco E, Carlblom N, Sharpe AL, Beckstead MJ, Wickman K. Selective Ablation of GIRK Channels in Dopamine Neurons Alters Behavioral Effects of Cocaine in Mice. Neuropsychopharmacology 2017 Feb;42(3):707-715. PMID: 27468917, PMCID: PMC5888879
Domínguez-López S, Howell RD, López-Canúl MG, Leyton M, Gobbi G. Electrophysiological characterization of dopamine neuronal activity in the ventral tegmental area across the light-dark cycle. Synapse 2014 Oct;68(10):454-67. PMID: 24955825
Domínguez-López S, Mahar I, Bambico FR, Labonté B, Ochoa-Sánchez R, Leyton M, Gobbi G. Short-term effects of melatonin and pinealectomy on serotonergic neuronal activity across the light-dark cycle. J Psychopharmacol 2012 Jun;26(6):830-44. PMID: 21730015
Domínguez-López S, Howell R, Gobbi G. Characterization of serotonin neurotransmission in knockout mice: implications for major depression. Rev Neurosci 2012;23(4):429-43. PMID: 23089640. Review
Contact
Aging & Metabolism Research Program, MS 21
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-7574
Fax: (405) 271-1437
E-mail: Sergio-dominguezlopez@omrf.org
