alexa The Anticonvulsant Tiagabine Inhibits Cocaineâ€Â
ISSN: 2167-0501

Biochemistry & Pharmacology: Open Access
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Review Article

The Anticonvulsant Tiagabine Inhibits Cocaine’s Rewarding Effects, but has No Effect on Reinstatement of Cocaine-Seeking Behavior in Rats

Hong-Ju Yang, Guo-Hua Bi, Haiying Zhang, Xiao-Qing Peng, Eliot L. Gardner, and Zheng-Xiong Xi*
Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA
Corresponding Author : Zheng-Xiong Xi
Intramural Research Program
National Institute on Drug Abuse
Baltimore, USA
Tel: +1 443-740-2517
E-mail: [email protected] nida.nih.gov
Received February 26, 2013; Accepted March 27, 2013; Published March 29, 2013
Citation: Yang HJ, Bi GH, Zhang H, Peng XQ, Xi ZX (2013) The Anticonvulsant Tiagabine Inhibits Cocaine’s Rewarding Effects, but has No Effect on Reinstatement of Cocaine-Seeking Behavior in Rats. Biochem Pharmacol (Los Angel) S1:005. doi:10.4172/2167-0501.S1-005
Copyright: © 2013 Yang HJ, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
 

Abstract

GABA is an important neurotransmitter involved in drug abuse and addiction. Accordingly, drugs that elevate brain GABA levels are thought to be promising for the treatment of addiction. In the present study, we report that tiagabine, a selective type 1 GABA transporter inhibitor that has been approved by the U.S. FDA as an anticonvulsant drug, may have therapeutic potential in reducing cocaine use. In vivo brain microdialysis studies demonstrated that systemic administration of tiagabine (3, 10, 20 mg/kg, i.p.) significantly elevated extracellular GABA levels in the nucleus accumbens in a dose-dependent manner. Pretreatment with tiagabine (3, 10 mg/kg, i.p.) significantly inhibited cocaine enhanced electrical brain-stimulation reward. Tiagabine alone, at 20 mg/kg, almost completely inhibited intracranial electrical brain-stimulation behavior. In addition, systemic administration of tiagabine (10, 20 mg/kg) also dose dependently inhibited intravenous cocaine self-administration, but had no effect on cocaine-induced reinstatement of drug-seeking behavior. These data suggest that: 1) elevation of brain GABA levels by tiagabine not only inhibits brain reward function but also attenuates cocaine’s rewarding effects, and 2) tiagabine or other GABA transporter inhibitors may have therapeutic effects in reducing cocaine use, but not in preventing relapse to drug-seeking behavior.

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