Mu Ying, Ren Zhaoxiang, Jia Jia, Gao Bo, Zheng Longtai, Wang Guanghui, Friedman Eitan, Zhen Xuechu
Mol Brain. 2014 Sep 25;7:70. doi: 10.1186/s13041-014-0070-1.
Phosphodiesterase (PDE) 10A is selectively expressed in medium spiny neurons of the striatum. Nucleus accumbens (NAc) is a key region that mediates drug reward and addiction-related behaviors. To investigate the potential role of PDE10A in the reinforcement properties of morphine, we tested the effect of MP-10, a selective inhibitor of PDE10A, on acquisition, expression, and extinction of morphine-induced conditioned place preference (CPP).
The results show that 2.5 mg/kg MP-10, administered subcutaneously, significantly inhibited the acquisition of morphine-induced CPP. The same dose of MP-10 alone did not result in the CPP. Moreover, MP-10 did not alter the expression of morphine-induced CPP, but did accelerate the extinction of morphine-induced CPP. Additionally, chronic treatment with 2.5 mg/kg MP-10 decreased expression of phosphorylated CREB (pCREB), activated cAMP response element binding protein, in dorsomedial striatum, in shell of NAc, and in anterior cingulate cortex (ACC) as well as decreased expression of ΔFosB in the shell of NAc and ACC.
The results suggest that inhibition of PDE10A may have therapeutic potential in the treatment of opioid addiction.
磷酸二酯酶（PDE）10A在纹状体的中等棘状神经元中选择性表达。伏隔核（NAc）是介导药物奖赏和成瘾相关行为的关键区域。为了研究PDE10A在吗啡强化特性中的潜在作用，我们测试了PDE10A的选择性抑制剂MP - 10对吗啡诱导的条件性位置偏爱（CPP）的获得、表达和消退的影响。
结果表明，皮下注射2.5mg/kg的MP - 10可显著抑制吗啡诱导的CPP的获得。相同剂量的MP - 10单独使用不会导致CPP。此外，MP - 10不会改变吗啡诱导的CPP的表达，但会加速吗啡诱导的CPP的消退。另外，2.5mg/kg的MP - 10慢性治疗可降低背内侧纹状体、NAc壳和前扣带回皮质（ACC）中磷酸化CREB（pCREB）的表达，pCREB即活化的环磷酸腺苷反应元件结合蛋白，同时也降低了NAc壳和ACC中ΔFosB的表达。
结果表明，抑制PDE10A可能在治疗阿片类成瘾方面具有治疗潜力。
