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Glutamate Transporter 1 in the Central Nervous System: Potential Target for the Treatment of Alcohol Dependence

Sreemantula, Sai Nandini

Abstract Details

2012, Master of Science in Pharmaceutical Science (MSP), University of Toledo, College of Pharmacy.
Alcohol dependence is characterized by compulsive alcohol use. Chronic alcohol consumption can lead to alterations of neurotransmitter systems. The Glutamatergic system is one of the neurotransmitter systems affected as a consequence of alcohol abuse. It is suggested that increased glutamate transmission in key brain regions of the mesocorticolimbic motive circuit may promote alcohol- seeking behavior due to its reinforcing effects. We hypothesize that activation or up-regulation of the glutamate transporter 1 (GLT 1), a major transporter responsible for most of glutamate uptake would reduce extracellular glutamate and consequently attenuate alcohol consumption. Ceftriaxone (CEF), a β lactam antibiotic, has previously been identified as a drug that can elevate GLT 1 expression and reduce alcohol consumption in alcohol-preferring (P) rats (Sari et al., 2011). In the present study, we further explored the differential effects of CEF in the prefrontal cortex (PFC) and subregions of nucleus accumbens (NAc) such as the core and shell. In order to confirm the effects of upregulation/activation of GLT 1 in the attenuation of alcohol consumption, we also tested GPI-1046, another compound known to increase GLT 1 expression. Alcohol consumption was significantly reduced in P rats treated with CEF 50 mg/kg, CEF 100 mg/kg, GPI 10 mg/kg and GPI 20 mg/kg intra-peritoneally as compared to saline treated groups. GPI-1046 had no effect on sucrose consumption. GLT 1 expression was down regulated in P rats exposed to alcohol as compared to naïve group, in the NAc core and shell areas but not in the PFC. Upregulation of GLT 1 was observed with CEF 100 mg/kg treatment in PFC, NAc core and NAc shell and with GPI 10 mg/kg and GPI 20 mg/kg treatments in PFC and NAc Core. These results provide substantial information about the role of GLT 1 as a potential target for the treatment of Alcohol dependence
Youssef Sari, PhD (Committee Chair)
William Messer, PhD (Committee Member)
Ezdihar Hassoun, PhD (Committee Member)
Zahoor Shah, PhD (Committee Member)
94 p.

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Citations

  • Sreemantula, S. N. (2012). Glutamate Transporter 1 in the Central Nervous System: Potential Target for the Treatment of Alcohol Dependence [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1333546775

    APA Style (7th edition)

  • Sreemantula, Sai. Glutamate Transporter 1 in the Central Nervous System: Potential Target for the Treatment of Alcohol Dependence. 2012. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1333546775.

    MLA Style (8th edition)

  • Sreemantula, Sai. "Glutamate Transporter 1 in the Central Nervous System: Potential Target for the Treatment of Alcohol Dependence." Master's thesis, University of Toledo, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=mco1333546775

    Chicago Manual of Style (17th edition)