Deletion of Type 2 Metabotropic Glutamate Receptor Decreases Sensitivity to Cocaine Reward in Rats

Hong Ju Yang, Hai Ying Zhang, Guo Hua Bi, Yi He, Jun Tao Gao, Zheng Xiong Xi

Research output: Contribution to journalArticlepeer-review

Abstract

Cocaine users show reduced expression of the metabotropic glutamate receptor (mGluR2), but it is not clear whether this is a predisposing trait for addiction or a consequence of drug exposure. In this study, we found that a nonsense mutation at the mGluR2 gene decreased mGluR2 expression and altered the seeking and taking of cocaine. mGluR2 mutant rats show reduced sensitivity to cocaine reward, requiring more cocaine to reach satiation when it was freely available and ceasing their drug-seeking behavior sooner than controls when the response requirement was increased. mGluR2 mutant rats also show a lower propensity to relapse after a period of cocaine abstinence, an effect associated with reduced cocaine-induced dopamine and glutamate overflow in the nucleus accumbens. These findings suggest that mGluR2 polymorphisms or reduced availability of mGluR2 might be risk factors for the initial development of cocaine use but could actually protect against addiction by reducing sensitivity to cocaine reward.

Original languageEnglish (US)
Pages (from-to)319-332
Number of pages14
JournalCell Reports
Volume20
Issue number2
DOIs
StatePublished - Jul 11 2017

Keywords

  • NMDA receptor
  • addiction
  • autoreceptor
  • cocaine reward
  • dopamine
  • etiology of addiction
  • glutamate
  • mGluR2
  • relapse
  • self-administration

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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