Differential involvement of GABAA and GABAB receptors in propofol self-administration in rats

Aim: Propofol has shown abuse potential. The aim of the present study is to investigate the effects of GABA(A) antagonist and GABA(B) agonist on propofol reinforcement. Methods: Sprague-Dawley rats were trained to self-administer propofol at a dose of 1.7 mg/kg per infusion under a fixed ratio (FR1) schedule of reinforcement for 14 d. In a separate set of experiments, food-maintained self-administration under a fixed ratio (FR5) schedule and locomotor activities of Sprague-Dawley rats were examined. Results: GABA(A) receptor antagonist bicuculline (0.25 mg/kg, ip) significantly increased the number of injections and active responses. Pretreatment with GABA(B) receptor agonist baclofen (3 mg/kg, ip) significantly decreased the number of active responses and total infusions of propofol during the training session. Moreover, microinjection of baclofen (50 and 100 ng/side) into the ventral tegmental area (VTA) significantly decreased the number of active responses and total infusions of propofol. Neither baclofen (1-3 mg/kg, ip) nor bicuculline (0.25-1 mg/kg, ip) affected food-maintained responses or motor activities. Conclusion: Propofol maintains its reward properties partially through GABA(A) receptor activation. Stimulation of GABA(B) receptors in VTA may counteract the reinforcing properties of propofol.