Background 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). Results 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 ?FosB in the shell of NAc and ACC. Conclusion The results suggest that inhibition of PDE10A may have therapeutic potential in the treatment of opioid addiction.
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机译：背景技术磷酸二酯酶（PDE）10A在纹状体的中刺神经元中选择性地表达。 Nucleumens（NAC）是一个介导药物奖励和成瘾行为的关键区域。为了研究PDE10A在吗啡的增强性质中的潜在作用，我们测试了MP-10，PDE10A的选择性抑制剂，在吗啡诱导的条件偏好（CPP）的射击。结果结果表明，皮下给药2.5mg / kg mp-10显着抑制了吗啡诱导的CPP的获取。单独的MP-10同一剂量没有导致CPP。此外，MP-10没有改变吗啡诱导的CPP的表达，但确实加速了吗啡诱导的CPP的消失。另外，慢性处理2.5mg / kg MP-10降低了磷酸化CreB（PCREB），活化的阵营响应元件结合蛋白，在NAC的壳中，在NAC壳中的表达，并且在前铰接皮质（ACC）以及减少的表达中of？fosb在nac和acc的壳中。结论结果表明，PDE10A的抑制可能具有治疗阿片类药物成瘾的治疗潜力。
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