Role of CB2 receptors in social and aggressive behavior in male mice

Abstract

Rationale

Male CB1KO mice exhibit stronger aggressive responses than wild-type mice.

Objective

This study was designed to examine the role of cannabinoid CB2r in social and aggressive behavior.

Methods

The social interaction test and resident–intruder paradigm were performed in mice lacking CB2r (CB2KO) and in wild-type (WT) littermates. The effects of the CB2r selective agonist JWH133 (1 and 2 mg/kg) on aggression were also evaluated in Oncins France 1 (OF1) mice. Gene expression analyses of monoamine oxidase-A (MAO-A), catechol-o-methyltransferase (COMT), 5-hydroxytryptamine transporter (5-HTT), and 5-HT1B receptor (5HT1Br) in the dorsal raphe nuclei (DR) and the amygdala (AMY) were carried out using real-time PCR.

Results

Group-housed CB2KO mice exhibited higher levels of aggression in the social interaction test and displayed more aggression than resident WT mice. Isolation increased aggressive behavior in WT mice but did not affect CB2KO animals; however, the latter mice exhibited higher levels of social interaction with their WT counterparts. MAO-A and 5-HTT gene expression was significantly higher in grouped CB2KO mice. The expression of 5HT1Br, COMT, and MAO-A in the AMY was more pronounced in CB2KO mice than in WT counterparts. Acute administration of the CB2 agonist JWH133 significantly reduced the level of aggression in aggressive isolated OF1 mice, an effect that decreased after pretreatment with the CB2 receptor antagonist AM630.

Conclusion

Our results suggest that CB2r is implicated in social interaction and aggressive behavior and deserves further consideration as a potential new target for the management of aggression.

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Acknowledgments

This work was supported by the following research grants: Ministerio de Ciencia e Innovación (SAF2011-23420 awarded to Jorge Manzanares; SAF2010-15793 awarded to Olga Valverde); Ministerio de Economía y Competitividad, Dirección General de Investigación (PSI2011-24762 awarded to PI Jose Miñarro); Generalidad Valenciana, Consejería de Educación (PROMETEO/2009/072 awarded to PI Jose Miñarro); Generalitat de Catalunya (2009SGR684 awarded to Olga Valverde); Instituto de Salud “Carlos III” (FIS); Redes Telemáticas de Investigación Cooperativa en Salud (RETICS); Red de Trastornos Adictivos (RTA); fondos FEDER (RD06/0001/1004 and RD12/0028/0019 awarded to PI Jorge Manzanares, RD06/001/0016 and RD12/0028/0005 awarded to PI Jose Miñarro, and RD06/001/1001 and RD12/0028/0024 awarded to PI Olga Valverde).

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Correspondence to Marta Rodríguez-Arias.

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Highlights

- Grouped CB2KO mice show higher levels of offensive aggression than WT mice in the social interaction test.

- CB2KO mice show higher levels of offensive aggression than WT mice in the resident intruder paradigm.

- COMT, MAO-A, 5-HTT and 5HT1Br mRNA levels differ in WT and CB2KO mice.

- Administration of JWH133 decreases the level of aggression in OF1 mice.

- Treatment with JWH133 normalizes alterations of MAO-A and COMT gene expression in aggressive isolated mice.

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Rodríguez-Arias, M., Navarrete, F., Blanco-Gandia, M.C. et al. Role of CB2 receptors in social and aggressive behavior in male mice. Psychopharmacology 232, 3019–3031 (2015). https://doi.org/10.1007/s00213-015-3939-5

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Keywords

  • CB2KO mice
  • Social encounters
  • Resident–intruder paradigm
  • Aggression
  • OF1 mice
  • JWH133
  • Gene expression