A selective D3 receptor antagonist YQA14 attenuates methamphetamine-induced behavioral sensitization and conditioned place preference in mice.

Aim: We have reported that a selective dopamine D3 receptor antagonist YQA14 attenuates cocaine reward and relapse to drug-seeking in mice. In the present study, we investigated whether YQA14 could inhibit methamphetamine (METH)-induced locomotor sensitization and conditioned place preference (CPP) in mice.

Methods: Locomotor activity was monitored in mice treated with METH (1 mg/kg, ip) daily on d 4-13, followed by a challenge with METH (0.5 mg/kg) on d 21. CPP was examined in mice that were administered METH (1 mg/kg) or saline alternately on each other day for 8 days (METH conditioning). YQA14 was injected intraperitoneally 20 min prior to METH or saline.

Results: Both repetitive (daily on d 4-13) and a single injection (on the day of challenge) of YQA14 (6.25, 12.5 and 25 mg/kg) dose-dependently inhibited the acquisition and expression of METH-induced locomotor sensitization. However, repetitive injection of YQA14 (daily during the METH conditioning) did not alter the acquisition of METH-induced CPP, whereas a single injection of YQA14 (prior to CPP test) dose-dependently attenuated the expression of METH-induced CPP. In addition, the repetitive injection of YQA14 dose-dependently facilitated the extinction and decreased the reinstatement of METH-induced CPP.

Conclusion: Brain D3 receptors are critically involved in the reward and psychomotor-stimulating effects of METH. Thus, YQA14 deserves further study as a potential medication for METH addiction.