title: Activation of PKCzeta and PKMzeta in the nucleus accumbens core is necessary for the retrieval, consolidation and reconsolidation of drug memory.
abstract: One of the greatest challenges in the treatment of substance dependence is to reverse the control that drug-associated stimuli have gained over the addict's behavior, as these drug-associated memories increase the risk of relapse even after long periods of abstinence. We report here that inhibition of the atypical protein kinase C isoform PKCzeta and its constitutively active isoform PKMzeta with the pseudosubstrate inhibitor ZIP administered locally into the nucleus accumbens core reversibly inhibited the retrieval of drug-associated memory and drug (remifentanil) seeking, whereas a scrambled ZIP peptide or staurosporine, an effective inhibitor of c/nPKC-, CaMKII-, and PKA kinases that does not affect PKCzeta/PKMzeta activity, was without effect on these memory processes. Acquisition or extinction of drug-associated memory remained unaffected by PKCzeta- and PKMzeta inhibition.
authors.affiliation: Experimental Psychiatry Unit, Department of General Psychiatry and Social Psychiatry, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Crespo
authors.forename: Petra
authors.initials: P
authors.lastname: Stöckl
authors.forename: Florian
authors.initials: F
authors.lastname: Ueberall
authors.forename: Marcel
authors.initials: M
authors.lastname: Jenny
authors.forename: Alois
authors.initials: A
authors.lastname: Saria
authors.forename: Gerald
authors.initials: G
authors.lastname: Zernig
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008568:Memory; D009714:Nucleus Accumbens / Q000201:enzymology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D019966:Substance-Related Disorders / Q000209:etiology*; D000099221:Protein Kinase C zeta
chemical_list: D007527:Isoenzymes; D011493:Protein Kinase C; D000099221:Protein Kinase C zeta