title: DISC1 signaling in cocaine addiction: Towards molecular mechanisms of co-morbidity.
abstract: Substance abuse and other psychiatric diseases may share molecular pathology. In order to test this hypothesis, we examined the role of Disrupted In Schizophrenia 1 (DISC1), a psychiatric risk factor, in cocaine self-administration (SA). Cocaine SA significantly increased expression of DISC1 in the nucleus accumbens (NAc); while knockdown of DISC1 in NAc significantly increased cocaine SA and decreased phosphorylation of GSK-3β at Ser9 compared to scrambled shRNA. Our study provides the first mechanistic evidence of a critical role of DISC1 in drug-induced behavioral neuroadaptations and sheds more light at the shared molecular pathology of drug abuse and other major psychiatric disorders.
authors.affiliation: The State University of New York at Buffalo, Buffalo, NY, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Gancarz
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jouroukhin
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Saito
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, USA.
authors.forename: Alexey
authors.initials: A
authors.lastname: Shevelkin
authors.affiliation: The State University of New York at Buffalo, Buffalo, NY, USA.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Mueller
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kamiya
authors.affiliation: The State University of New York at Buffalo, Buffalo, NY, USA. Electronic address: ddietz@buffalo.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Dietz
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, USA; Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, USA; Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA. Electronic address: mpletni1@jhu.edu.
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Pletnikov
mesh_terms: D000818:Animals; D016739:Behavior, Addictive; D003042:Cocaine / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000523:psychology; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000378:metabolism; D010766:Phosphorylation; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D015398:Signal Transduction
chemical_list: C498795:Disc1 protein, rat; D009419:Nerve Tissue Proteins; D000071679:Glycogen Synthase Kinase 3 beta; D003042:Cocaine
keywords: Co-morbidity; Cocaine; DISC1; Drug abuse; Psychiatric disorders