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The role of dopamine receptors in methamphetamine-induced cognitive deficits

Gutierrez, Arnold

Abstract Details

2018, PhD, University of Cincinnati, Medicine: Neuroscience/Medical Science Scholars Interdisciplinary.
Methamphetamine (MA) is an addictive psychostimulant that produces cognitive impairment after prolonged use. Dopamine receptors in the neostriatum have been identified as targets for preventing MA-induced neurotoxicity, however no data exists that these protective effects translate to cognitive protection. Animal models of MA-induced cognitive deficits have been developed, however studies using the Morris water maze (MWM), which is an important model of hippocampal-based L&M, have produced mixed results. The aim of the present work is to examine the viability of targeting striatal dopamine receptors to protect against MA-induced L&M deficits in adult male rats. We first determined whether a large (244 cm in diameter) MWM would be capable of detecting MA effects after a 4 x 10 mg/kg MA at 2 h intervals dosing regimen and if housing affected these effects. Next, we assessed the ability of a single high dose (40 mg/kg) of MA in producing egocentric and allocentric L&M deficits and whether MA would shift strategic dominance. Finally, we tested whether pretreatment with dopamine D1 receptor (DRD1) or dopamine D2 receptor (DRD2) antagonists directly into the neostriatum prior to MA would attenuate MA-induced neurobehavioral deficits. We show that MA effects are detectable in the large MWM for both types of dosing strategies and that a single high dose of MA produces deficits in egocentric and allocentric navigation as well as prevents a consistent navigation strategy from being utilized. We also demonstrate attenuation by both types of antagonists on MA-evoked deficits in egocentric and allocentric L&M and on striatal dopamine depletion. To our knowledge, this is the first report showing attenuation of MA-induced cognitive effects by blockade of dopamine receptors in the striatum.
Michael Williams, Ph.D. (Committee Chair)
Gary Gudelsky, Ph.D. (Committee Member)
Renu Sah, Ph.D. (Committee Member)
Kim Seroogy, Ph.D. (Committee Member)
Charles Vorhees, Ph.D. (Committee Member)
256 p.

Recommended Citations

Citations

  • Gutierrez, A. (2018). The role of dopamine receptors in methamphetamine-induced cognitive deficits [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1521189209471948

    APA Style (7th edition)

  • Gutierrez, Arnold. The role of dopamine receptors in methamphetamine-induced cognitive deficits. 2018. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1521189209471948.

    MLA Style (8th edition)

  • Gutierrez, Arnold. "The role of dopamine receptors in methamphetamine-induced cognitive deficits." Doctoral dissertation, University of Cincinnati, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1521189209471948

    Chicago Manual of Style (17th edition)