title: Inhibition of phosphodiesterase10A attenuates morphine-induced conditioned place preference.
abstract: 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 ΔFosB in the shell of NAc and ACC.
  
  
  CONCLUSIONS
  The results suggest that inhibition of PDE10A may have therapeutic potential in the treatment of opioid addiction.
authors.forename: Ying
authors.initials: Y
authors.lastname: Mu
authors.forename: Zhaoxiang
authors.initials: Z
authors.lastname: Ren
authors.forename: Jia
authors.initials: J
authors.lastname: Jia
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.forename: Longtai
authors.initials: L
authors.lastname: Zheng
authors.forename: Guanghui
authors.initials: G
authors.lastname: Wang
authors.forename: Eitan
authors.initials: E
authors.lastname: Friedman
authors.forename: Xuechu
authors.initials: X
authors.lastname: Zhen
mesh_terms: D000818:Animals; D002755:Choice Behavior / Q000187:drug effects*; D003213:Conditioning, Psychological / Q000187:drug effects*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C483820:Fosb protein, rat; D016760:Proto-Oncogene Proteins c-fos; D009020:Morphine; C512064:PDE10A protein, rat; D010727:Phosphoric Diester Hydrolases