Biochimie & Pharmacologie : Libre accès
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Abstrait

Today in Psychopharmacology and Neuropharmacology

Jie Wu

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 cocaineenhanced 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 dosedependently 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.