Nucleus Accumbens Drd1-Expressing Neurons Control Aggression Self-Administration and Aggression Seeking in Mice.
Level 5 - mechanism / opinion, no new human data
Level 5 by CEBM rules (preclinical animal experiment).
PubMed 30655356 · doi:10.1523/JNEUROSCI.2409-18.2019
What was done
Adult male outbred CD-1 mice were trained in an operant aggression self-administration paradigm (9 days, 12 trials per day) where lever-pressing provided access to attack subordinate intruder male mice, followed by testing for self-administration and aggression seeking on abstinence Day 1. Neuronal activation in the nucleus accumbens (NAc core and shell) was assessed by measuring the activity marker Fos and its colocalization with dopamine receptor D1 (*Drd1*) and D2 (*Drd2*) using immunohistochemistry and in situ hybridization. To test causality, hybrid mice generated from outbred CD-1 and inbred *Drd1*-Cre or *Drd2*-Cre lines received Cre-dependent inhibitory DREADDs (hM4Di) to selectively silence Drd1- or Drd2-expressing NAc neurons during testing.
What was found
Aggression self-administration and seeking induced greater Fos expression in the NAc shell than in the NAc core, with Fos colocalizing with both *Drd1*- and *Drd2*-expressing neurons in both subregions. Chemogenetic silencing of NAc Drd1-expressing neurons reduced aggression self-administration and aggression seeking, whereas silencing Drd2-expressing neurons did not alter either behavior. Exact numerical values and effect sizes were not reported in the abstract.
Why it matters
These findings identify NAc Drd1-expressing neurons as a key neural substrate mediating appetitive aggression reward and relapse behaviors. The study also validates a hybrid breeding approach enabling cell-type-specific genetic manipulations in outbred mouse models of aggression.
Limits
Findings are restricted to an animal model using exclusively adult male mice; findings cannot be assumed to generalize to females or humans. Exact animal sample sizes and quantitative effect sizes are not reported in the abstract. The study only examined seeking behavior at acute abstinence (Day 1), leaving longer-term abstinence dynamics unaddressed.
Cited by
- supports Animals will work for the opportunity to engage in aggressive fighting behavior.