Article
Increased novelty-induced locomotion, sensitivity to amphetamine, and extracellular dopamine in striatum of Zdhhc15-deficient mice
Author/s | Mejías Estévez, Rebeca María
Rodríguez Gotor, Juan J. Niwa, Minae Krasnova, Irina N. Adamczyk, Abby Han, Mei Wang, Tao |
Department | Universidad de Sevilla. Departamento de Fisiología |
Publication Date | 2021 |
Deposit Date | 2022-05-19 |
Published in |
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Abstract | 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. ... 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. |
Funding agencies | National Institutes of Health. United States |
Project ID. | R21NS085358
RO1HD052680 RO1MH112808 R21NS085358 |
Citation | Mejías Estévez, R.M., Rodríguez Gotor, J.J., Niwa, M., Krasnova, I.N., Adamczyk, A., Han, M. y Wang, T. (2021). Increased novelty-induced locomotion, sensitivity to amphetamine, and extracellular dopamine in striatum of Zdhhc15-deficient mice. Translational Psychiatry, 11 (1), 65. |
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