DISC1 signaling in cocaine addiction: Towards molecular mechanisms of co-morbidity

Amy Gancarz, Yan Jouroukhin, Atsushi Saito, Alexey Shevelkin, Lauren E. Mueller, Atsushi Kamiya, David M. Dietz, Mikhail Pletnikov

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalNeuroscience Research
DOIs
StateAccepted/In press - Jul 14 2015

Fingerprint

Cocaine-Related Disorders
Self Administration
Schizophrenia
Cocaine
Morbidity
Psychiatry
Molecular Pathology
Nucleus Accumbens
Substance-Related Disorders
Glycogen Synthase Kinase 3
Small Interfering RNA
Phosphorylation
Pharmaceutical Preparations

Keywords

  • Co-morbidity
  • Cocaine
  • DISC1
  • Drug abuse
  • Psychiatric disorders

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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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.",
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AU - Jouroukhin, Yan

AU - Saito, Atsushi

AU - Shevelkin, Alexey

AU - Mueller, Lauren E.

AU - Kamiya, Atsushi

AU - Dietz, David M.

AU - Pletnikov, Mikhail

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