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5-HT1B receptors, ventral orbitofrontal cortex, and aggressive behavior in mice

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Abstract

Rationale

Systemic injections of 5-HT1B receptor agonists have been shown to have specific anti-aggressive effects in aggressive individuals. One site of action for these drugs is the 5-HT1B receptors in the ventral orbitofrontal cortex (VO PFC), an area that has been implicated in the inhibitory control of behavior and is a terminal region for 5-HT projections.

Objective

To assess the anti-aggressive effects of the 5-HT1B receptor agonist CP-94,253 when microinjected into the VO PFC (0.1, 0.56, and 1.0 μg/0.2 μl) or into the infralimbic prefrontal cortex (IL PFC; 1.0 μg/0.2 μl) in separate groups of aggressive resident male mice. To confirm the 5-HT1B receptor as the critical site of action for the anti-aggressive effects, the 5-HT1B/D antagonist GR-127,935 was microinjected at 10.0 μg/0.2 μl into the VO PFC. After recovery from surgery, the anti-aggressive effects of microinjected CP-94,253 were studied during 5-min resident–intruder confrontations that were recorded and analyzed.

Results

Microinjections of CP-94,253 (0.56 and 1.0 μg/0.2 μl) dose-dependently reduced the frequency of attack bites and sideways threats. This effect was behaviorally specific because non-aggressive motor activities were not significantly altered by the drug. In the IL vmPFC or in an area lateral to the VO PFC, CP-94,253 (1.0 μg/0.2 μl) did not have significant behavioral effects.

Conclusions

The results highlight the 5-HT1B receptors in the VO PFC as a particularly important site for the inhibition of species-typical aggressive behavior in male mice.

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Acknowledgements

The authors would like to thank Mr. J. Thomas Sopko and Mr. Dirson João Stein for their outstanding technical support. This research was supported in part by UNISINOS, Universidade do Vale do Rio dos Sinos, RS, Brazil.

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Authors and Affiliations

  1. Laboratório de Neurociências, Universidade do Vale do Rio dos Sinos, UNISINOS, São Leopoldo, RS, Brazil

    R. M. M. De Almeida, M. M. Rosa, D. M. Santos, D. M. Saft & Q. Benini

  2. Department of Psychology, Bacon Hall, Tufts University, 530 Boston Avenue, Medford, MA, 02155, USA

    K. A. Miczek

  3. Department of Psychiatry, Tufts University, Boston, MA, USA

    K. A. Miczek

  4. Department of Pharmacology, Tufts University, Boston, MA, USA

    K. A. Miczek

  5. Department of Neuroscience, Tufts University, Boston, MA, USA

    K. A. Miczek

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  1. R. M. M. De Almeida
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De Almeida, R.M.M., Rosa, M.M., Santos, D.M. et al. 5-HT1B receptors, ventral orbitofrontal cortex, and aggressive behavior in mice. Psychopharmacology 185, 441–450 (2006). https://doi.org/10.1007/s00213-006-0333-3

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