Increased novelty-induced locomotion, sensitivity to amphetamine, and extracellular dopamine in striatum of Zdhhc15-deficient mice.
Increased novelty-induced locomotion, sensitivity to amphetamine, and extracellular dopamine in striatum of Zdhhc15-deficient mice.
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DOI：
10.1038/s41398-020-01194-6
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发表时间：
2021-01-18
影响因子：
6.8
通讯作者：
Wang T
中科院分区：
文献类型：
--
作者：
Mejias R;Rodriguez-Gotor JJ;Niwa M;Krasnova IN;Adamczyk A;Han M;Thomas GM;Xi ZX;Huganir RL;Pletnikov MV;Sawa A;Cadet JL;Wang T
Novelty-seeking behaviors and impulsivity are personality traits associated with several psychiatric illnesses including attention deficits hyperactivity disorders. The underlying neural mechanisms remain poorly understood. We produced and characterized a line of knockout mice for zdhhc15, which encodes a neural palmitoyltransferase. Genetic defects of zdhhc15 were implicated in intellectual disability and behavioral anomalies in humans. Zdhhc15-KO mice showed normal spatial learning and working memory but exhibited a significant increase in novelty-induced locomotion in open field. Striatal dopamine content was reduced but extracellular dopamine levels were increased during the habituation phase to a novel environment. Administration of amphetamine and methylphenidate resulted in a significant increase in locomotion and extracellular dopamine levels in the ventral striatum of mutant mice compared to controls. Number and projections of dopaminergic neurons in the nigrostriatal and mesolimbic pathways were normal. No significant change in the basal palmitoylation of known ZDHHC15 substrates including DAT was detected in striatum of zdhhc15 KO mice using an acyl-biotin exchange assay. These results support that a transient, reversible, and novelty-induced elevation of extracellular dopamine in ventral striatum contributes to novelty-seeking behaviors in rodents and implicate ZDHHC15-mediated palmitoylation as a novel regulatory mechanism of dopamine in the striatum.
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影响因子：
25.8
作者：
Chang, Zheng;Lichtenstein, Paul;Larsson, Henrik
通讯作者：
Larsson, Henrik
影响因子：
8.2
作者：
Faraone SV
通讯作者：
Faraone SV
影响因子：
4.2
作者：
Hornemann, Thorsten
通讯作者：
Hornemann, Thorsten
影响因子：
3.3
作者：
Ford CP
通讯作者：
Ford CP
影响因子：
16.6
作者：
Beard, Richard S., Jr.;Yang, Xiaoyuan;Meegan, Jamie E.;Overstreet, Jonathan W.;Yang, Clement G. Y.;Elliott, John A.;Reynolds, Jason J.;Cha, Byeong J.;Pivetti, Christopher D.;Mitchell, David A.;Wu, Mack H.;Deschenes, Robert J.;Yuan, Sarah Y.
通讯作者：
Yuan, Sarah Y.