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5-HT1B receptor inhibition of alcohol-heightened aggression in mice: comparison to drinking and running

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Abstract

Rationale

Serotonin 5-HT1B receptors are promising targets for the management of several mood and impulse disorders.

Objective

These experiments examine a 5-HT1B agonist, CP-94,253, and attempt to distinguish between its effects on seeking to perform three rewarding behaviors: aggression, drinking, and wheel running.

Materials and methods

Male CFW mice perform nose-poke responses that are maintained by a fixed interval schedules of 10-min (FI10) schedule to gain access to one of three rewarding activities. The first experiment studies mice reinforced by the opportunity to confront an intruder mouse after drinking water or alcohol; the second studies mice reinforced by the presentation of alcoholic or non-alcoholic solutions (i.e., 6% ethanol, 0.05% saccharin vs 0.05% saccharin); the third studies mice reinforced by access to a running wheel.

Results

CP-94,253 (1.0–10 mg/kg i.p.) dose-dependently reduces aggression, drinking, and wheel running. Of these behaviors, alcohol-heightened aggression is the most sensitive to the 5-HT1B receptor agonist (ED50 = 4.8 mg/kg). Responding for the opportunity to drink or engage in alcohol-heightened aggression is suppressed by the highest dose of CP-94,253, whereas CP-94,253 does not affect responding that is reinforced by wheel running or species-typical aggression.

Conclusions

These results confirm the inhibitory effects of 5-HT1B receptor stimulation on aggressive performance and drinking. They also reveal an inhibition of voluntary wheel running, contrary to the stimulation of running in a novel, open arena. 5-HT1B receptor agonists may be particularly useful for the treatment of aggressive behavioral disorders, but their efficacy and potency appear to be sensitive to the intensity and context of the behavior.

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Acknowledgment

For their significant contributions to the execution of these experiments, the authors extend their gratitude to Jeremy Maggin, Airlia Esworthy, Jamie Golden, and Adam Chu. The authors also appreciate the exemplary technical assistance of Mr. J. Thomas Sopko. This research was supported by USPHS grant (AA013983) from NIAAA (KAM).

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Authors and Affiliations

  1. Department of Psychology, Tufts University, 530 Boston Ave. (Bacon Hall), Medford, MA, USA

    Eric W. Fish, Sara D. McKenzie-Quirk, Makoto Bannai & Klaus A. Miczek

  2. Department of Psychiatry, Tufts University, 530 Boston Ave. (Bacon Hall), Medford, MA, 02155, USA

    Klaus A. Miczek

  3. Department of Pharmacology, Tufts University, 530 Boston Ave. (Bacon Hall), Medford, MA, USA

    Klaus A. Miczek

  4. Department of Neuroscience, Tufts University, 530 Boston Ave. (Bacon Hall), Medford, MA, USA

    Klaus A. Miczek

  5. Research Institute for Health Fundamentals, Ajinomoto Co., Inc., Kawasaki, Japan

    Makoto Bannai

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  1. Eric W. Fish
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  2. Sara D. McKenzie-Quirk
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  3. Makoto Bannai
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  4. Klaus A. Miczek
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Correspondence to Klaus A. Miczek.

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Fish, E.W., McKenzie-Quirk, S.D., Bannai, M. et al. 5-HT1B receptor inhibition of alcohol-heightened aggression in mice: comparison to drinking and running. Psychopharmacology 197, 145–156 (2008). https://doi.org/10.1007/s00213-007-1017-3

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  • DOI: https://doi.org/10.1007/s00213-007-1017-3

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