期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 13, 页码 3476-3481出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1719897115
关键词
parvalbumin; DRD2; psychosis; mouse; deletion
资金
- Agencia Nacional de Promocion Cientifica y Tecnologica (ANPCYT) [PICT 2013-0182, PICT 2015-0364, PICT 2012-2024]
- FOCEM-MERCOSUR [COF 03711]
- Fundacion Roemmers
- Fundacion Florencio Fiorini
- Consejo Nacional de Investigaciones Cientificas y Tecnicas
- ANPCYT
- Fundacion Bunge y Born
Excessive dopamine neurotransmission underlies psychotic episodes as observed in patients with some types of bipolar disorder and schizophrenia. The dopaminergic hypothesis was postulated after the finding that antipsychotics were effective to halt increased dopamine tone. However, there is little evidence for dysfunction within the dopaminergic system itself. Alternatively, it has been proposed that excessive afferent activity onto ventral tegmental area dopaminergic neurons, particularly from the ventral hippocampus, increase dopamine neurotransmission, leading to psychosis. Here, we show that selective dopamine D-2 receptor deletion from parvalbumin interneurons in mouse causes an impaired inhibitory activity in the ventral hippocampus and a dysregulated dopaminergic system. Conditional mutant animals show adult onset of schizophrenia-like behaviors and molecular, cellular, and physiological endophenotypes as previously described from postmortem brain studies of patients with schizophrenia. Our findings show that dopamine D-2 receptor expression on parvalbumin interneurons is required to modulate and limit pyramidal neuron activity, which may prevent the dysregulation of the dopaminergic system.
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