Homer proteins regulate sensitivity to cocaine

Karen K. Szumlinski, Marlin H. Dehoff, Shin H. Kang, Kelly A. Frys, Kevin D. Lominac, Matthias Klugmann, Jason Rohrer, William Griffin, Shigenobu Toda, Nicolas P. Champtiaux, Thomas Berry, Jian C. Tu, Stephanie E. Shealy, Matthew J. During, Lawrence D. Middaugh, Paul F. Worley, Peter W. Kalivas

Research output: Contribution to journalArticle

Abstract

Drug addiction involves complex interactions between pharmacology and learning in genetically susceptible individuals. Members of the Homer gene family are regulated by acute and chronic cocaine administration. Here, we report that deletion of Homer1 or Homer2 in mice caused the same increase in sensitivity to cocaine-induced locomotion, conditioned reward, and augmented extracellular glutamate in nucleus accumbens as that elicited by withdrawal from repeated cocaine administration. Moreover, adeno-associated virus-mediated restoration of Homer2 in the accumbens of Homer2 KO mice reversed the cocaine-sensitized phenotype. Further analysis of Homer2 KO mice revealed extensive additional behavioral and neurochemical similarities to cocaine-sensitized animals, including accelerated acquisition of cocaine self-administration and altered regulation of glutamate by metabotropic glutamate receptors and cystine/glutamate exchange. These data show that Homer deletion mimics the behavioral and neurochemical phenotype produced by repeated cocaine administration and implicate Homer in regulating addiction to cocaine.

Original languageEnglish (US)
Pages (from-to)401-413
Number of pages13
JournalNeuron
Volume43
Issue number3
DOIs
StatePublished - Aug 5 2004

ASJC Scopus subject areas

  • Neuroscience(all)

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    Szumlinski, K. K., Dehoff, M. H., Kang, S. H., Frys, K. A., Lominac, K. D., Klugmann, M., Rohrer, J., Griffin, W., Toda, S., Champtiaux, N. P., Berry, T., Tu, J. C., Shealy, S. E., During, M. J., Middaugh, L. D., Worley, P. F., & Kalivas, P. W. (2004). Homer proteins regulate sensitivity to cocaine. Neuron, 43(3), 401-413. https://doi.org/10.1016/j.neuron.2004.07.019