The melanin-concentrating hormone system modulates cocaine reward

Shinjae Chung, F. Woodward Hopf, Hiroshi Nagasaki, Chun Ying Li, James D. Belluzzi, Antonello Bonci, Olivier Civelli

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Drug addiction is mediated by complex neuronal processes that converge on the shell of the nucleus accumbens (NAcSh). The NAcSh receives inputs from the lateral hypothalamus (LH), where self-stimulation can be induced. Melanin-concentrating hormone (MCH) is produced mainly in the LH, and its receptor (MCH1R) is highly expressed in the NAcSh. We found that, in the NAcSh, MCH1R is coexpressed with dopamine receptors (D1R and D2R), and that MCH increases spike firing when both D1R and D2R are activated. Also, injecting MCH potentiates cocaine-induced hyperactivity in mice. Mice lacking MCH1R exhibit decreased cocaine-induced conditioned place preference, as well as cocaine sensitization. Using a specific MCH1R antagonist, we further show that acute blockade of the MCH system not only reduces cocaine self-administration, but also attenuates cue- and cocaine-induced reinstatement. Thus, the MCH system has an important modulatory role in cocaine reward and reinforcement by potentiating the dopaminergic system in the NAcSh, which may provide a new rationale for treating cocaine addiction.

Original languageEnglish
Pages (from-to)6772-6777
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number16
DOIs
Publication statusPublished - 21-04-2009

All Science Journal Classification (ASJC) codes

  • General

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