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Ceftriaxone reduces alcohol intake in outbred rats while upregulating xCT in the nucleus accumbens core.
Pharmacol Biochem Behav 2017; 159:18-23PB

Abstract

Alcohol addiction is a chronic disease characterized by an inability to regulate drinking. A critical brain region involved in alcohol consumption is the nucleus accumbens (NA). Glutamate transmission in this region regulates alcohol consumption and relapse to alcohol-seeking. Across multiple alcohol-administration rodent models, basal extracellular glutamate levels are increased in the NA during early withdrawal. Glutamate transporter 1 (GLT-1) and system xC-, containing the subunit xCT, regulate NA glutamate levels. Ceftriaxone (Cef) increases expression and function of both transporters following extinction from cocaine self-administration and here we sought to determine if Cef would similarly decrease alcohol consumption while increasing xCT and GLT-1 in the NA core. We used the intermittent access to alcohol (IAA) paradigm to induce drinking in outbred Sprague-Dawley rats; this paradigm permits rats access to alcohol (20%v/v) for 24-h without water deprivation, followed by 24-h of abstinence. Following 17 24-h drinking sessions, Cef treatment (200mg/kg IP) was initiated and continued for 5days while a control group received vehicle (0.9% saline IP). Alcohol consumption was assessed for two 24-h periods during Cef and two 24-h periods after cessation of Cef treatment. In a separate cohort of rats, Cef's ability to alter blood alcohol levels (BALs) after a non-contingent alcohol injection (1g/kg) was assessed. We found that Cef decreased alcohol consumption during the period of Cef treatment and on the two days following injections, and this was accompanied by an increase in NA core xCT expression. Furthermore, a history of alcohol consumption did not alter xCT and GLT-1 expression relative to alcohol-naïve controls. Cef did not alter BALs, indicating that the reduction in alcohol consumption was not caused by altered alcohol clearance. These results indicate that while Cef reduces alcohol consumption in outbred rats, its ability to do so is not associated with an increase in GLT-1 expression.

Authors+Show Affiliations

Psychology Department, University of Florida, Gainesville, FL, United States. Electronic address: bstennett@ufl.edu.Psychology Department, University of Florida, Gainesville, FL, United States.Department of Pharmacodynamics, University of Florida, Gainesville, FL, United States.Psychology Department, University of Florida, Gainesville, FL, United States.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28687200

Citation

Stennett, Bethany A., et al. "Ceftriaxone Reduces Alcohol Intake in Outbred Rats While Upregulating xCT in the Nucleus Accumbens Core." Pharmacology, Biochemistry, and Behavior, vol. 159, 2017, pp. 18-23.
Stennett BA, Frankowski JC, Peris J, et al. Ceftriaxone reduces alcohol intake in outbred rats while upregulating xCT in the nucleus accumbens core. Pharmacol Biochem Behav. 2017;159:18-23.
Stennett, B. A., Frankowski, J. C., Peris, J., & Knackstedt, L. A. (2017). Ceftriaxone reduces alcohol intake in outbred rats while upregulating xCT in the nucleus accumbens core. Pharmacology, Biochemistry, and Behavior, 159, pp. 18-23. doi:10.1016/j.pbb.2017.07.001.
Stennett BA, et al. Ceftriaxone Reduces Alcohol Intake in Outbred Rats While Upregulating xCT in the Nucleus Accumbens Core. Pharmacol Biochem Behav. 2017;159:18-23. PubMed PMID: 28687200.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ceftriaxone reduces alcohol intake in outbred rats while upregulating xCT in the nucleus accumbens core. AU - Stennett,Bethany A, AU - Frankowski,Jan C, AU - Peris,Joanna, AU - Knackstedt,Lori A, Y1 - 2017/07/04/ PY - 2017/03/19/received PY - 2017/06/19/revised PY - 2017/07/03/accepted PY - 2017/7/9/pubmed PY - 2018/5/22/medline PY - 2017/7/9/entrez KW - Addiction KW - GLT-1 KW - Glutamate KW - System x(C)− KW - xCT SP - 18 EP - 23 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol. Biochem. Behav. VL - 159 N2 - Alcohol addiction is a chronic disease characterized by an inability to regulate drinking. A critical brain region involved in alcohol consumption is the nucleus accumbens (NA). Glutamate transmission in this region regulates alcohol consumption and relapse to alcohol-seeking. Across multiple alcohol-administration rodent models, basal extracellular glutamate levels are increased in the NA during early withdrawal. Glutamate transporter 1 (GLT-1) and system xC-, containing the subunit xCT, regulate NA glutamate levels. Ceftriaxone (Cef) increases expression and function of both transporters following extinction from cocaine self-administration and here we sought to determine if Cef would similarly decrease alcohol consumption while increasing xCT and GLT-1 in the NA core. We used the intermittent access to alcohol (IAA) paradigm to induce drinking in outbred Sprague-Dawley rats; this paradigm permits rats access to alcohol (20%v/v) for 24-h without water deprivation, followed by 24-h of abstinence. Following 17 24-h drinking sessions, Cef treatment (200mg/kg IP) was initiated and continued for 5days while a control group received vehicle (0.9% saline IP). Alcohol consumption was assessed for two 24-h periods during Cef and two 24-h periods after cessation of Cef treatment. In a separate cohort of rats, Cef's ability to alter blood alcohol levels (BALs) after a non-contingent alcohol injection (1g/kg) was assessed. We found that Cef decreased alcohol consumption during the period of Cef treatment and on the two days following injections, and this was accompanied by an increase in NA core xCT expression. Furthermore, a history of alcohol consumption did not alter xCT and GLT-1 expression relative to alcohol-naïve controls. Cef did not alter BALs, indicating that the reduction in alcohol consumption was not caused by altered alcohol clearance. These results indicate that while Cef reduces alcohol consumption in outbred rats, its ability to do so is not associated with an increase in GLT-1 expression. SN - 1873-5177 UR - https://www.unboundmedicine.com/medline/citation/28687200/Ceftriaxone_reduces_alcohol_intake_in_outbred_rats_while_upregulating_xCT_in_the_nucleus_accumbens_core_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-3057(17)30185-5 DB - PRIME DP - Unbound Medicine ER -