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

作　　者：Li SUN Rui SONG Ying CHEN Ri-fang YANG Ning WU Rui-bin SU Jin LI 

机构地区：[1]epartment of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China [2]Department of Anesthesiology, General Hospital of Beijing Military Command, Belling 100700, China [3]State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China [4]Beijing Key Laboratory of Neuropsychopharmacology, Beijing 100850, China

出　　处：《Acta Pharmacologica Sinica》2016年第2期157-165,共9页中国药理学报（英文版）

基　　金：This work was supported by the Natural Science Foundation of China （No 81102425）, a project of the National Science and Technology Support Program in China （2012BAI01B07） andBeijing Nova Program xx2014A014, the Key Project of Natural Science Foundation of Beijing （7131010） and the National Basic Research Program of China （No 2009CB522008）.

摘　　要：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.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.

关 键 词：drug addiction METHAMPHETAMINE YQA14 dopamine D3 receptor  locomotor sensitization  conditioned place preference REINSTATEMENT 

分 类 号：R9[医药卫生—药学]