Jordi Bonaventura Morea, Ph.D.

@article{Gomez2017,

title = {Chemogenetics revealed: DREADD occupancy and activation via converted clozapine.},

author = {Juan L Gomez and Jordi Bonaventura and Wojciech Lesniak and William B Mathews and Polina Sysa-Shah and Lionel A Rodriguez and Randall J Ellis and Christopher T Richie and Brandon K Harvey and Robert F Dannals and Martin G Pomper and Antonello Bonci and Michael Michaelides},

url = {https://www.ncbi.nlm.nih.gov/pubmed/28774929},

doi = {10.1126/science.aan2475},

issn = {1095-9203 (Electronic); 0036-8075 (Linking)},

year  = {2017},

date = {2017-08-04},

urldate = {2017-08-04},

journal = {Science},

volume = {357},

number = {6350},

pages = {503--507},

address = {Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit, National Institute on Drug Abuse (NIDA) Intramural Research Program, Baltimore, MD 21224, USA.},

abstract = {The chemogenetic technology DREADD (designer receptors exclusively activated by designer drugs) is widely used for remote manipulation of neuronal activity in freely moving animals. DREADD technology posits the use of "designer receptors," which are exclusively activated by the "designer drug" clozapine N-oxide (CNO). Nevertheless, the in vivo mechanism of action of CNO at DREADDs has never been confirmed. CNO does not enter the brain after systemic drug injections and shows low affinity for DREADDs. Clozapine, to which CNO rapidly converts in vivo, shows high DREADD affinity and potency. Upon systemic CNO injections, converted clozapine readily enters the brain and occupies central nervous system-expressed DREADDs, whereas systemic subthreshold clozapine injections induce preferential DREADD-mediated behaviors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@article{Bonaventura2015,

title = {Allosteric interactions between agonists and antagonists within the adenosine A_{2A} receptor-dopamine D_{2} receptor heterotetramer},

author = {Jordi Bonaventura and Gemma Navarro and Veronica Casadó-Anguera and Karima Azdad and William Rea and Estefania Moreno and Marc Brugarolas and Josefa Mallol and Enric I Canela and Carme Lluis and Antoni Cortés and Nora D Volkow and Serge N Schiffmann and Sergi Ferré and Vicent Casadó},

url = {http://www.pnas.org/content/112/27/E3609.abstract

http://www.pnas.org/content/early/2015/06/17/1507704112},

doi = {10.1073/pnas.1507704112},

year  = {2015},

date = {2015-06-22},

journal = {Proceedings of the National Academy of Sciences},

volume = {112},

number = {27},

pages = {E3609-E3618},

abstract = {Adenosine A_{2A} receptor (A_{2A}R)-dopamine D_{2} receptor (D_{2}R) heteromers are key modulators of striatal neuronal function. It has been suggested that the psychostimulant effects of caffeine depend on its ability to block an allosteric modulation within the A_{2A}R-D_{2}R heteromer, by which adenosine decreases the affinity and intrinsic efficacy of dopamine at the D_{2}R. We describe novel unsuspected allosteric mechanisms within the heteromer by which not only A_{2A}R agonists, but also A_{2A}R antagonists, decrease the affinity and intrinsic efficacy of D_{2}R agonists and the affinity of D_{2}R antagonists. Strikingly, these allosteric modulations disappear on agonist and antagonist coadministration. This can be explained by a model that considers A_{2A}R-D_{2}R heteromers as heterotetramers, constituted by A_{2A}R and D_{2}R homodimers, as demonstrated by experiments with bioluminescence resonance energy transfer and bimolecular fluorescence and bioluminescence complementation. As predicted by the model, high concentrations of A_{2A}R antagonists behaved as A_{2A}R agonists and decreased D_{2}R function in the brain. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}