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

Katherine M Nautiyal; Kenji F Tanaka; Mary M Barr; Laurent Tritschler; Yannick Le Dantec; Denis J David; Alain M Gardier; Carlos Blanco; René Hen; Susanne E Ahmari

doi:10.1016/j.neuron.2015.03.041

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

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

Authors

Affiliations

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Actins / genetics
Actins / metabolism
Aggression / physiology*
Animals
Animals, Newborn
Brain / anatomy & histology*
Brain / growth & development
Brain / metabolism
Choice Behavior / physiology
Conditioning, Operant / drug effects
Conditioning, Operant / physiology
Dopamine / metabolism
Dopamine Uptake Inhibitors / pharmacology
Doxycycline / pharmacology
Gene Expression Regulation, Developmental / drug effects
Gene Expression Regulation, Developmental / genetics
Gene Expression Regulation, Developmental / physiology*
Impulsive Behavior / physiology*
Iodine Isotopes / pharmacokinetics
Mice
Mice, Transgenic
Pindolol / analogs & derivatives
Pindolol / pharmacokinetics
Piperazines / pharmacology
Protein Binding / drug effects
Receptor, Serotonin, 5-HT1B / genetics
Receptor, Serotonin, 5-HT1B / metabolism*
Serotonin / metabolism
Serotonin Antagonists / pharmacokinetics

Substances

Actins
Dopamine Uptake Inhibitors
Iodine Isotopes
Piperazines
Receptor, Serotonin, 5-HT1B
Serotonin Antagonists
Serotonin
cyanopindolol
vanoxerine
Pindolol
Doxycycline
Dopamine

Abstract

Publication types

MeSH terms

Substances

Grants and funding