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Neuron. 2015 May 6;86(3):813-26. doi: 10.1016/j.neuron.2015.03.041. Epub 2015 Apr 16.

Distinct Circuits Underlie the Effects of 5-HT1B Receptors on Aggression and Impulsivity.

Author information

1
Department of Psychiatry, Columbia University, New York, NY 10032, USA; Division of Integrative Neuroscience, the New York State Psychiatric Institute, New York, NY 10032, USA.
2
Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo 160 8582, Japan.
3
Department of Psychiatry, Columbia University, New York, NY 10032, USA.
4
Université Paris-Sud, INSERM UMR-S 1178, Faculté de Pharmacie, Université Paris-Saclay, Châtenay-Malabry 92296, France.
5
Department of Psychiatry, Columbia University, New York, NY 10032, USA; Division of Integrative Neuroscience, the New York State Psychiatric Institute, New York, NY 10032, USA; Department of Neuroscience, Columbia University, New York, NY 10032, USA. Electronic address: rh95@columbia.edu.
6
Department of Psychiatry, Translational Neuroscience Program, Center for Neuroscience Program, Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA 15219, USA. Electronic address: ahmarise@upmc.edu.

Abstract

Impulsive and aggressive behaviors are both modulated by serotonergic signaling, specifically through the serotonin 1B receptor (5-HT1BR). 5-HT1BR knockout mice show increased aggression and impulsivity, and 5-HT1BR polymorphisms are associated with aggression and drug addiction in humans. To dissect the mechanisms by which the 5-HT1BR affects these phenotypes, we developed a mouse model to spatially and temporally regulate 5-HT1BR expression. Our results demonstrate that forebrain 5-HT1B heteroreceptors expressed during an early postnatal period contribute to the development of the neural systems underlying adult aggression. However, distinct heteroreceptors acting during adulthood are involved in mediating impulsivity. Correlating with the impulsivity, dopamine in the nucleus accumbens is elevated in the absence of 5-HT1BRs and normalized following adult rescue of the receptor. Overall, these data show that while adolescent expression of 5-HT1BRs influences aggressive behavior, a distinct set of 5-HT1B receptors modulates impulsive behavior during adulthood.

PMID:
25892302
PMCID:
PMC4431594
DOI:
10.1016/j.neuron.2015.03.041
[Indexed for MEDLINE]
Free PMC Article

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