# Role of lateral habenula orexin receptor signaling in aggressive social behavior

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $526,936

## Abstract

Abstract: Abnormal social behavior, such as maladaptive aggression or social anxiety to a lack of interest in
social relationships, is associated with a number of neuropsychiatric disorders including schizophrenia, mood
disorders and autism. Such disruptions in social behavior are thought to result, in part, from inappropriate
activation of brain reward systems in response to social stimuli. A series of nuclei within the ventral midbrain
that control mood and emotion are known to encode certain aspects of aggressive and nonaggressive social
interaction; however, little is known about the neural circuit mechanisms that directly modulate the motivational
or rewarding component of social behavior. To address this question, we established a mouse behavioral
model for investigating individual differences in social behavior. In this model, approximately 70% of outbred
mice engage in aggressive behavior with a resident intruder and find such interaction rewarding, whereas the
remaining 30% are not aggressive at all and find intruder interactions aversive. The lateral habenula (LHb) is a
major hub within the brain's reward circuit and can encode information about positive and negative social
stimuli. Interestingly, the LHb is differentially activated by intruder-based social interaction in aggressive and
nonaggressive mice and we hypothesize that it plays a critical role in mediating social behavior. Indeed, our
preliminary results show that the neuropeptide, orexin (also known as hypocretin) signals directly within the
LHb to control initiation of aggressive social behavior and the valence of social interaction during the resident
intruder paradigm in aggressive mice. In this application, we will dissect the complex microcircuitry of the LHb
using cell type specific molecular tools to control orexin receptor signaling along with in vivo monitoring of
neural activity in awake behaving animals to understand LHb function in social behavior. A basic
understanding of these circuits is absolutely critical for developing new treatment strategies for social deficits in
a range of psychiatric illnesses.

## Key facts

- **NIH application ID:** 10197012
- **Project number:** 5R01MH114882-05
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** SCOTT JAMES RUSSO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $526,936
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197012

## Citation

> US National Institutes of Health, RePORTER application 10197012, Role of lateral habenula orexin receptor signaling in aggressive social behavior (5R01MH114882-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10197012. Licensed CC0.

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