Featured Paper of the Month – March 2017
Bonaventura, Jordi; Quiroz, Cesar; Cai, Ning-Sheng; Rubinstein, Marcelo; Tanda, Gianluigi; Ferre, Sergi
Key role of the dopamine D4 receptor in the modulation of corticostriatal glutamatergic neurotransmission. Journal Article
In: Sci Adv, vol. 3, no. 1, pp. e1601631, 2017, ISSN: 2375-2548 (Electronic); 2375-2548 (Linking).
@article{Bonaventura2017,
title = {Key role of the dopamine D_{4} receptor in the modulation of corticostriatal glutamatergic neurotransmission.},
author = {Jordi Bonaventura and Cesar Quiroz and Ning-Sheng Cai and Marcelo Rubinstein and Gianluigi Tanda and Sergi Ferre},
url = {https://www.ncbi.nlm.nih.gov/pubmed/28097219},
doi = {10.1126/sciadv.1601631},
issn = {2375-2548 (Electronic); 2375-2548 (Linking)},
year = {2017},
date = {2017-01-01},
journal = {Sci Adv},
volume = {3},
number = {1},
pages = {e1601631},
address = {Integrative Neurobiology Section, National Institute on Drug Abuse, Intramural research Program, National Institutes of Health, Baltimore, MD 21224, USA.},
abstract = {Polymorphic variants of the dopamine D4 receptor gene (DRD4) have been repeatedly associated with numerous neuropsychiatric disorders. Yet, the functional role of the D4 receptor and the functional differences of the products of DRD4 polymorphic variants remained enigmatic. Immunohistochemical and optogenetic-microdialysis experiments were performed in knock-in mice expressing a D4 receptor with the long intracellular domain of a human DRD4 polymorphic variant associated with attention deficit hyperactivity disorder (ADHD). When compared with the wild-type mouse D4 receptor, the expanded intracellular domain of the humanized D4 receptor conferred a gain of function, blunting methamphetamine-induced cortical activation and optogenetic and methamphetamine-induced corticostriatal glutamate release. The results demonstrate a key role of the D4 receptor in the modulation of corticostriatal glutamatergic neurotransmission. Furthermore, these data imply that enhanced D4 receptor-mediated dopaminergic control of corticostriatal transmission constitutes a vulnerability factor of ADHD and other neuropsychiatric disorders.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Polymorphic variants of the dopamine D4 receptor gene (DRD4) have been repeatedly associated with numerous neuropsychiatric disorders. Yet, the functional role of the D4 receptor and the functional differences of the products of DRD4 polymorphic variants remained enigmatic. Immunohistochemical and optogenetic-microdialysis experiments were performed in knock-in mice expressing a D4 receptor with the long intracellular domain of a human DRD4 polymorphic variant associated with attention deficit hyperactivity disorder (ADHD). When compared with the wild-type mouse D4 receptor, the expanded intracellular domain of the humanized D4 receptor conferred a gain of function, blunting methamphetamine-induced cortical activation and optogenetic and methamphetamine-induced corticostriatal glutamate release. The results demonstrate a key role of the D4 receptor in the modulation of corticostriatal glutamatergic neurotransmission. Furthermore, these data imply that enhanced D4 receptor-mediated dopaminergic control of corticostriatal transmission constitutes a vulnerability factor of ADHD and other neuropsychiatric disorders.
