Studies support the involvement of mPFC dopaminergic and glutamatergic systems in the development of cocaine sensitization. GABA is known to modulate dopamine and glutamatergic systems in the mPFC. In addition, recent reports have suggested that cocaine sensitization might be associated with a decrease in GABAB receptor responsiveness in the mPFC. Hence, in vivo microdialysis of the mPFC was performed to examine the effects on extracellular GABA levels within the mPFC of a cocaine challenge subsequent to repeated cocaine administration. Male Sprague-Dawley rats were given four daily injections of saline (1.0 mL/kg, i.p.) or cocaine (15 mg/kg, i.p.) and challenged with the same dose of saline or cocaine 1, 7 or 28 days later. Acute cocaine produced a motor-stimulant response that was significantly augmented in repeated cocaine animals at all withdrawal time points. Moreover, sensitized animals exhibited a significant increase in extracellular GABA levels after 1 and 7 days but not 28 days following repeated cocaine exposure. These data suggest that cocaine-induced sensitization is associated with a transient increase in mPFC GABA transmission.