Cell-Type-Specific Role of ΔFosB in Nucleus Accumbens In Modulating Intermale Aggression.

TitleCell-Type-Specific Role of ΔFosB in Nucleus Accumbens In Modulating Intermale Aggression.
Publication TypeJournal Article
Year of Publication2018
AuteursAleyasin, H, Flanigan, ME, Golden, SA, Takahashi, A, Menard, C, Pfau, ML, Multer, J, Pina, J, McCabe, KA, Bhatti, N, Hodes, GE, Heshmati, M, Neve, RL, Nestler, EJ, Heller, EA, Russo, SJ
JournalJ Neurosci
Volume38
Issue26
Pagination5913-5924
Date Published2018 06 27
ISSN1529-2401
KeywordsAggression, Animals, Behavior, Animal, Male, Mice, Mice, Transgenic, Neurons, Nucleus Accumbens, Proto-Oncogene Proteins c-fos, Reward
Abstract

A growing number of studies implicate the brain's reward circuitry in aggressive behavior. However, the cellular and molecular mechanisms within brain reward regions that modulate the intensity of aggression as well as motivation for it have been underexplored. Here, we investigate the cell-type-specific influence of ΔFosB, a transcription factor known to regulate a range of reward and motivated behaviors, acting in the nucleus accumbens (NAc), a key reward region, in male aggression in mice. We show that ΔFosB is specifically increased in dopamine D1 receptor (Drd1)-expressing medium spiny neurons (D1-MSNs) in NAc after repeated aggressive encounters. Viral-mediated induction of ΔFosB selectively in D1-MSNs of NAc intensifies aggressive behavior without affecting the preference for the aggression-paired context in a conditioned place preference (CPP) assay. In contrast, ΔFosB induction selectively in D2-MSNs reduces the time spent exploring the aggression-paired context during CPP without affecting the intensity of aggression per se. These data strongly support a dissociable cell-type-specific role for ΔFosB in the NAc in modulating aggression and aggression reward. Aggressive behavior is associated with several neuropsychiatric disorders and can be disruptive for affected individuals as well as their victims. Studies have shown a positive reinforcement mechanism underlying aggressive behavior that shares many common features with drug addiction. Here, we explore the cell-type-specific role of the addiction-associated transcription factor ΔFosB in the nucleus accumbens in aggression. We found that ΔFosB expression promotes aggressive behavior, effects that are dissociable from its effects on aggression reward. This finding is a significant first step in identifying therapeutic targets for the reduction of aggressive behavior across a range of neuropsychiatric illnesses.

DOI10.1523/JNEUROSCI.0296-18.2018
Alternate JournalJ. Neurosci.
PubMed ID29891732
PubMed Central IDPMC6021989
Grant ListR01 MH104559 / MH / NIMH NIH HHS / United States
F31 MH105217 / MH / NIMH NIH HHS / United States
F30 MH100835 / MH / NIMH NIH HHS / United States
T32 MH087004 / MH / NIMH NIH HHS / United States
R37 DA007359 / DA / NIDA NIH HHS / United States
P50 MH096890 / MH / NIMH NIH HHS / United States
R01 MH114882 / MH / NIMH NIH HHS / United States
R01 MH090264 / MH / NIMH NIH HHS / United States
P50 AT008661 / AT / NCCIH NIH HHS / United States
T32 MH096678 / MH / NIMH NIH HHS / United States