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To fight or not to fight: activation of the mPFC during decision to engage in aggressive behavior after ethanol consumption in a novel murine model

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Abstract

Rationale

Alcohol consumption is a common antecedent of aggressive behavior. The effects of alcohol on the decision to engage in aggression in preference over pro-social interaction are hypothesized to arise from augmented function within the medial prefrontal cortex (mPFC).

Objective

In a newly developed procedure, we studied social decision-making in male C57BL/6 J mice based on preferentially seeking access to either sociosexual interactions with a female partner or the opportunity to attack an intruder male. While deciding to engage in aggressive vs. sociosexual behavior, corresponding neural activation was assessed via c-Fos immunoreactivity in cortical, amygdaloid and tegmental regions of interest. A further objective was to investigate how self-administered alcohol impacted social choice.

Methods

During repeated confrontations with an intruder male in their home cage, experimental mice engaged in species-specific sequence of pursuit, threat, and attack behavior within < 2 min. Mice were then conditioned to respond at one of two separate illuminated operanda in an experimental chamber (octagon) attached to their home cage; completion of 10 responses (fixed ratio 10; FR10) was reinforced by access to either a female or a male intruder which were presented in the resident’s home cage. Brains were harvested following choice between the concurrently available aggressive and sociosexual options and processed for c-Fos immunoreactivity across 10 brain regions. In two separate groups, mice were trained to rapidly self-administer ethanol prior to a social choice trial in order to examine the effects of alcohol on social choice, sociosexual, aggressive acts and postures, and concurrent c-Fos activity in the mPFC and limbic regions.

Results and discussion

Eight out of 65 mice consistently chose to engage in aggressive behavior in preference to sociosexual contact with a female when each outcome was concurrently available. Self-administered alcohol (experiment 1: 1.2 ± 0.02 g/kg; experiment 2: 0, 1.0, 1.5, and 1.8 g/kg) increased responding for the aggressive option in mice that previously opted predominantly for access to sociosexual interactions with the female. When choosing the aggressive, but not the sociosexual option, the prelimbic area of the mPFC revealed increased c-Fos activity, guiding future detailed inquiry into the neural mechanisms for aggressive choice.

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Acknowledgements

The authors would like to thank J. Thomas Sopko, J. Kissel, W. Hsu, M. Perry, K. Hazzard, Chelsea Ty, and Natalie Kane for their assistance. Denis Dupuis and Scott MacCorkle from the machine shop expertly developed and constructed the new octagon apparatus.

Funding

This work was funded by NIH grants AA013983 and DA031734 (KAM, PI).

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Authors and Affiliations

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

    Klaus A. Miczek, Naz Akdilek, Vania M. M. Ferreira, Michael Z. Leonard, Lillian R. Marinelli & Herbert E. Covington III

  2. Department of Neuroscience, Tufts University, Boston, MA, 02111, USA

    Klaus A. Miczek

  3. Universidade de Brasilea, Instituto de Psicologia, Brasilia, Brazil

    Vania M. M. Ferreira

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  1. Klaus A. Miczek
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  2. Naz Akdilek
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Correspondence to Klaus A. Miczek.

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Footnote

We dedicate this report to Chris-Ellyn Johanson for her pioneering studies on choice.

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Miczek, K.A., Akdilek, N., Ferreira, V.M.M. et al. To fight or not to fight: activation of the mPFC during decision to engage in aggressive behavior after ethanol consumption in a novel murine model. Psychopharmacology 239, 3249–3261 (2022). https://doi.org/10.1007/s00213-022-06208-3

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