Rapid CommunicationDISC1 signaling in cocaine addiction: Towards molecular mechanisms of co-morbidity

- Cocaine self-administration up-regulates DISC1 expression in the nucleus accumbens.
- DISC1 knockdown in the nucleus accumbens increases cocaine self-administration.
- DISC1 knockdown in the nucleus accumbens decreases GSK-3β phosphorylation.
- Substance abuse and other psychiatric disorders may share molecular pathology.

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.