Methylphenidate administration promotes sociability and reduces aggression in a mouse model of callousness

Abstract

Rationale

Deficits in empathy constitute a distinctive feature of several psychopathologies, including conduct disorder (CD). The co-occurrence of callous-unemotional (CU) traits, excess rates of aggression and violation of societal norms confers specific risk for adult psychopathy. To date, the off-label use of methylphenidate (MPH) constitutes the drug treatment of choice.

Objectives

Herein, we tested the therapeutic potential of MPH in a recently devised mouse model recapitulating the core phenotypic abnormalities of CD.

Methods

Two subgroups of BALB/cJ male mice exhibiting opposite profiles of emotional contagion (i.e. socially transmitted adoption of another’s emotional states) were investigated for reactive aggression, sociability, attention control, anxiety-related behaviours and locomotor activity, in response to MPH administration (0.0, 3.0 or 6.0 mg/kg).

Results

Our data indicate that mice selected for excess callousness exhibit phenotypic abnormalities isomorphic to the symptoms of CD: stability of the low emotional contagion trait, increased aggression and reduced sociability. In accordance with our predictions, MPH reduced aggression and increased sociability in callous mice; yet, it failed to restore the low responsiveness to the emotions of a conspecific in pain, isomorphic to CU traits.

Conclusions

Although our data support the notion that MPH may contribute to the management of excess aggression in CD patients, additional studies shall identify specific treatments to target the callousness domain. The latter, unaffected by MPH in our experimental model, demands focused consideration whereby it constitutes a specifier associated with a worse prognosis.

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Acknowledgments

We wish to thank Flavia Chiarotti for statistical advice, Giulia Doria for precious collaboration throughout the execution of the experiments, Luigia Cancemi for valuable assistance with animal care and Stella Falsini for administrative support.

Funding

This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 603016 (project MATRICS). This paper reflects only the author’s views and the European Union is not liable for any use that may be made of the information contained therein.

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Correspondence to Francesca Zoratto or Giovanni Laviola.

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All experimental procedures were approved by Institutional Animal Survey Board on behalf of the Italian Ministry of Health (licence no. 409/2018-PR to G. Laviola) and performed in full accordance with the Directive 2010/63/EU on the protection of animals used for scientific purposes and Italian law (Legislative Decree 26/2014).

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Zoratto, F., Franchi, F., Macrì, S. et al. Methylphenidate administration promotes sociability and reduces aggression in a mouse model of callousness. Psychopharmacology 236, 2593–2611 (2019). https://doi.org/10.1007/s00213-019-05229-9

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Keywords

  • Callous-unemotional traits
  • Conduct disorder
  • Psychopathy
  • Empathy for pain
  • Methylphenidate