Searching for neural and behavioral parameters that predict anti-aggressive effects of chronic SSRI treatment in rats

Rationale: Only a subset of impulsive aggressive patients benefits from selective serotonin reuptake inhibitor (SSRI) treatment, confirming contradictory results about the association between serotonin (5-hydroxytryptamine, 5-HT) and aggression. This shows the need to define behavioral characteristics within this subgroup to move towards individualized pharmacological treatment of impulsive aggression.Methods: Here we submitted an outbred strain of Long Evans rats to a crossover design treatment regimen with the SSRI citalopram, to test its anti-aggressive effect. Behavioral characteristics were baseline aggression, anxiety parameters as measured in the elevated plus maze and open field and cue responsivity as indicated by sign vs. goal tracking behavior. 5-HT1A receptor densities as measured by ex vivo [F-18]MPPF binding were determined in the dorsal raphe nucleus, dentate gyrus, orbitofrontal cortex, infralimbic cortex and prelimbic cortex, because of the receptors' involvement in the therapeutic delay of SSRIs and aggression.Results: We found statistically significant increased variance in aggressive behavior after citalopram treatment. However, none of the selected parameters predicted the citalopram treatment effect.Conclusion: Since aggression after citalopram treatment decreased in a subgroup of animals and increased in the other, future research should focus on other possible predictors to support treatment strategies in aggressive patients.