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.