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Cocaine‐ and amphetamine‐regulated transcript peptide in the nucleus accumbens shell inhibits cocaine‐induced locomotor sensitization to transient over‐expression of α‐Ca 2+ /calmodulin‐dependent protein kinase II
Author(s) -
Xiong Lixia,
Meng Qing,
Sun Xi,
Lu Xiangtong,
Fu Qiang,
Peng Qinghua,
Yang Jianhua,
Oh KiWan,
Hu Zhenzhen
Publication year - 2018
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14289
Subject(s) - nucleus accumbens , sensitization , chemistry , pharmacology , cart , dopamine , protein kinase a , microbiology and biotechnology , medicine , endocrinology , phosphorylation , biology , neuroscience , biochemistry , mechanical engineering , engineering
Cocaine‐ and amphetamine‐regulated transcript ( CART ) peptide is a widely distributed neurotransmitter that attenuates cocaine‐induced locomotor activity when injected into the nucleus accumbens ( NA c). Our previous work first confirmed that the inhibitory mechanism of the CART peptide on cocaine‐induced locomotor activity is related to a reduction in cocaine‐enhanced phosphorylated Ca 2+ /calmodulin‐dependent protein kinase II α ( pCaMKII α) and the enhancement of cocaine‐induced D3R function. This study investigated whether CART peptide inhibited cocaine‐induced locomotor activity via inhibition of interactions between pCaMKII α and the D3 dopamine receptor (D3R). We demonstrated that lentivirus‐mediated gene transfer transiently increased pCaMKII α expression, which peaked at 10 days after microinjection into the rat NA c shell, and induced a significant increase in Ca 2+ influx along with greater behavioral sensitivity in the open field test after intraperitoneal injections of cocaine (15 mg/kg). However, western blot analysis and coimmunoprecipitation demonstrated that CART peptide treatment in lentivirus‐transfected Ca MKII α‐over‐expressing NA c rat tissues or cells prior to cocaine administration inhibited the cocaine‐induced Ca 2+ influx and attenuated the cocaine‐increased pCaMKII α expression in lentivirus‐transfected Ca MKII α‐over‐expressing cells. CART peptide decreased the cocaine‐enhanced phosphorylated cAMP response element binding protein ( pCREB ) expression via inhibition of the pCaMKII α‐D3R interaction, which may account for the prolonged locomotor sensitization induced by repeated cocaine treatment in lentivirus‐transfected Ca MKII α‐over‐expressing cells. These results provide strong evidence for the inhibitory modulation of CART peptide in cocaine‐induced locomotor sensitization.Cover Image for this issue: doi: 10.1111/jnc.14187 .