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Infralimbic and dorsal raphé microinjection of the 5-HT1B receptor agonist CP-93,129: attenuation of aggressive behavior in CFW male mice

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Abstract

Rationale

Aggressive behavior and impaired impulse control have been associated with dysregulations in the serotonergic system and with impaired functioning of the prefrontal cortex. 5-HT1B receptors have been shown to specifically modulate several types of offensive aggression.

Objective

This study aims to characterize the relative importance of two populations of 5-HT1B receptors in the dorsal raphé nucleus (DRN) and infralimbic cortex (ILC) in the modulation of aggressive behavior.

Methods

Male CFW mice were conditioned on a fixed-ratio 5 schedule of reinforcement to self-administer a 6% (w/v) alcohol solution. Mice repeatedly engaged in 5-min aggressive confrontations until aggressive behavior stabilized. Next, a cannula was implanted into either the DRN or the ILC. After recovery, mice were tested for aggression after self-administration of either 1.0 g/kg alcohol or water prior to a microinjection of the 5-HT1B agonist, CP-93,129 (0–1.0 μg/infusion).

Results

In both the DRN and ILC, CP-93,129 reduced aggressive behaviors after both water and alcohol self-administration. Intra-raphé CP-93,129 dose-dependently reduced both aggressive and locomotor behaviors. However, the anti-aggressive effects of intra-cortical CP-93,129 were behaviorally specific.

Conclusions

These findings highlight the importance of the serotonergic system in the modulation of aggression and suggest that the behaviorally specific effects of 5-HT1B receptor agonists are regionally selective. 5-HT1B receptors in a medial subregion of the prefrontal cortex, the ILC, appear to be critically involved in the attenuation of species-typical levels of aggression.

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Acknowledgments

The authors would like to thank J Thomas Sopko for his outstanding technical assistance. All research was supported by AA13983 (KAM)

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Authors and Affiliations

  1. Department of Psychology, Tufts University, Medford, MA, 02155, USA

    S. Faccidomo, I. M. H. Quadros, A. Takahashi, E. W. Fish & K. A. Miczek

  2. Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, CB #7178, Thurston Bowles Building, Chapel Hill, NC, 27599, USA

    S. Faccidomo

  3. Mouse Genomics Resource Laboratory, National Institute of Genetics, Mishima, Shizuoka, 411-8540, Japan

    A. Takahashi

  4. Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    E. W. Fish

  5. Departments of Psychiatry, Pharmacology and Experimental Therapeutics, and Neuroscience, Tufts University, Boston, MA, 02118, USA

    K. A. Miczek

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  1. S. Faccidomo
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Correspondence to S. Faccidomo.

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Faccidomo, S., Quadros, I.M.H., Takahashi, A. et al. Infralimbic and dorsal raphé microinjection of the 5-HT1B receptor agonist CP-93,129: attenuation of aggressive behavior in CFW male mice. Psychopharmacology 222, 117–128 (2012). https://doi.org/10.1007/s00213-011-2629-1

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