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June 12, 2018

Addicted to Aggression? Brain Protein May Hold the Answer

Aggressive behavior and the motivation to act aggressively have distinct molecular bases, according to a study of male mice. This finding suggests the possibility of reducing aggression by targeting a protein associated with addiction in a reward region of the brain. [Hossein Aleyasin/Icahn School of Medicine at Mount Sinai]

  • With apologies to Homer Simpson, we might prepare ourselves to hear, “It’s true! I’m an aggression-holic! I just can get enough aggression-hol!” Such a confession would be in keeping with a new neuroscientific finding—a protein known to accumulate in the brain’s reward center in response to pleasurable experiences, such as sex and other “highs,” also appears to be associated with aggression.

    Of course, the protein isn’t called aggression-hol. Instead, it is ΔFosB, a transcription factor known to regulate a range of reward and motivated behaviors. According to scientists based at the Perelman School of Medicine at the University of Pennsylvania and the Icahn School of Medicine at Mount Sinai, ΔFosB expression has distinct roles in two different cell types in the nucleus accumbens (NAc)—regulating aggressive behavior and its rewarding qualities.

    The scientists presented their work June 11 in the Journal of Neuroscience, in an article entitled “Cell-Type-Specific Role of ΔFosB in Nucleus Accumbens in Modulating Inter-Male Aggression.” In this article, the scientists describe how they began their work by showing that ΔFosB is specifically increased in dopamine D1 receptor (Drd1)-expressing medium spiny neurons (D1-MSNs) in the NAc after repeated aggressive encounters. The scientists also report on what happened after they induced ΔFosB in different cell populations.

    “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,” the article’s authors wrote. “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.”

    Essentially, the scientists found that ΔFosB expression promotes aggressive behavior, effects that are dissociable from its effects on aggression reward. “This finding,” the scientists noted, “is a significant first step in identifying therapeutic targets for the reduction of aggressive behavior across a range of neuropsychiatric illnesses.”

    Mount Sinai’s Scott Russo, Ph.D., the University of Pennsylvania’s Elizabeth Heller, Ph.D., and colleagues found that higher levels of ΔFosB in NAc neurons were associated with more intense behaviors by aggressive mice defending their home cage from an intruder. Overexpressing ΔFosB in aggressive mice also increased their dominance over an opponent when they faced each other in a narrow tube.

    While increased ΔFosB in D1-MSNs was associated with increased aggression intensity, mice with increased ΔFosB in D2-MSNs showed less preference for an environment where they previously encountered an intruder. The bottom line: Aggressive behavior and the motivation to act aggressively have distinct molecular bases.

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