Clin Psychopharmacol Neurosci.  2020 May;18(2):188-202. 10.9758/cpn.2020.18.2.188.

Contemporary Pharmacotherapeutics and the Management of Aggressive Behavior in an Adolescent Animal Model of Maladaptive Aggression

Affiliations
  • 1Department of Psychology, Northeastern University, Boston, MA, USA
  • 2Department of Program in Behavioral Neuroscience, Northeastern University, Boston, MA, USA

Abstract


Objective
Antipsychotic and anticonvulsant medications are increasingly being used as pharmacotherapeutic treatments for maladaptive aggression in youth, yet no information is available regarding whether these drugs exhibit aggressionspecific suppression in preclinical studies employing adolescent animal models of maladaptive aggression. This study examined whether the commonly used antipsychotics medications haloperidol and risperidone and the anticonvulsant medication valproate exert selective aggression-suppressing effects using a validated adolescent animal model of maladaptive aggression.
Methods
Twenty-seven-day old Syrian hamsters (Mesocricetus auratus) were administered testosterone for 30 consecutive days during the first 4 weeks of adolescent development. The following day (during late adolescence), experimental animals received a single dose of haloperidol (0.00, 0.025, 0.50, 1.0 mg/kg), risperidone (0.00, 0.01, 0.03, 1.0 mg/kg), or valproate (0.00, 1.0, 5.0, 10.0 mg/kg) and tested for offensive aggression using the Resident/Intruder Paradigm. As a baseline, non-aggressive behavioral control, a separate set of pubertal hamsters was treated with sesame oil vehicle during the first 4 weeks of adolescence and then tested for aggression during late adolescence in parallel with the haloperidol, risperidone or valproate-treated experimental animals.
Results
Risperidone and valproate selectively reduced the highly impulsive and intense maladaptive aggressive phenotype in a dose-dependent fashion. While haloperidol marginally reduced aggressive responding, its effects were non-specific as the decrease in aggression was concurrent with reductions in a several ancillary (non-aggressive) behaviors.
Conclusion
These studies provide pre-clinical evidence that the contemporary pharmacotherapeutics risperidone and valproate exert specific aggression-suppressing effects in an adolescent animal model of maladaptive aggression.

Keyword

Adolescent; Aggression; Antipsychotic agents; Anticonvulsants; Pharmacotherapy
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