Inhibition of the cyclooxygenase pathway attenuates morphine-induced conditioned place preference in mice

Prostanoids are shown to be important lipid mediators, not only in periphery but also in the brain, where they appear to modulate synaptic transmission. Recent studies have demonstrated that cyclooxygenase (COX) pathway might modulate the neurotransmission of gamma-aminobutyric acid and dopamine in the central nervous system. In this study, we have evaluated the effects of indomethacin (a non-selective COX inhibitor) and celecoxib (a selective COX-2 inhibitor) on the acquisition of morphine-induced conditioned place preference (CPP) in male Swiss mice. Our data shows that morphine (2.5-7.5 mg/kg) induces place preference conditioning in a dose-dependent manner. Celecoxib (0.01-5 mg/kg) and indomethacin (1 mg/kg) fail to produce a significant CPP or conditioned place aversion (CPA); however, higher doses of celecoxib (10 mg/kg) and indomethacin (5 mg/kg) induce CPA. Co-administration of celecoxib (0.5-5 mg/kg) or indomethacin (1-5 mg/kg) with morphine during the conditioning phase, blocked the acquisition of morphine CPP. These results indicate that the reward properties of morphine can be modulated by inhibiting COX activity in mice.