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J Neurochem. 2018 Aug;146(3):289-303. doi: 10.1111/jnc.14289. Epub 2018 May 4.

Cocaine- and amphetamine-regulated transcript peptide in the nucleus accumbens shell inhibits cocaine-induced locomotor sensitization to transient over-expression of α-Ca2+ /calmodulin-dependent protein kinase II.

Author information

1
Department of Pathophysiology, College of Basic Medicine, Nanchang University, Nanchang, Jiangxi, China.
2
Queen Mary Institute, School of Medicine, Nanchang University, Nanchang, Jiangxi, China.
3
Anhui Sinobioway Cell Therapy CO., LTD, Hefei, Anhui, China.
4
Department of Respiration, The Fourth Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China.
5
Department of Respiration, Department Two, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China.
6
Department of Anesthesiology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China.
7
Department of Physiology, College of Basic Medicine, Nanchang University, Nanchang, Jiangxi, China.
8
College of Pharmacy, Chungbuk National University, Cheongju, Korea.
9
Jiangxi Province Key laboratory of Tumor Pathogens and Molecular Pathology and the Department of Pathology, Schools of Basic Medical Sciences and Pharmaceutical Sciences, Nanchang University Medical College, Nanchang, China.

Abstract

Cocaine- and amphetamine-regulated transcript (CART) peptide is a widely distributed neurotransmitter that attenuates cocaine-induced locomotor activity when injected into the nucleus accumbens (NAc). 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 Ca2+ /calmodulin-dependent protein kinaseIIα (pCaMKIIα) and the enhancement of cocaine-induced D3R function. This study investigated whether CART peptide inhibited cocaine-induced locomotor activity via inhibition of interactions between pCaMKIIα and the D3 dopamine receptor (D3R). We demonstrated that lentivirus-mediated gene transfer transiently increased pCaMKIIα expression, which peaked at 10 days after microinjection into the rat NAc shell, and induced a significant increase in Ca2+ 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 CaMKIIα-over-expressing NAc rat tissues or cells prior to cocaine administration inhibited the cocaine-induced Ca2+ influx and attenuated the cocaine-increased pCaMKIIα expression in lentivirus-transfected CaMKIIα-over-expressing cells. CART peptide decreased the cocaine-enhanced phosphorylated cAMP response element binding protein (pCREB) expression via inhibition of the pCaMKIIα-D3R interaction, which may account for the prolonged locomotor sensitization induced by repeated cocaine treatment in lentivirus-transfected CaMKIIα-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.

KEYWORDS:

pCREB ; CART peptide; cocaine; locomotor sensitization; nucleus accumbens; pCaMKIIα-D3R interaction

PMID:
29313985
DOI:
10.1111/jnc.14289

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