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Repeated positive fighting experience in male inbred mice

Nature Protocols volume 9, pages 2705–2717 (2014)Cite this article

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Abstract

Repeated aggression is a frequent symptom of many psychiatric and neurological disorders, including obsessive-compulsive and attention deficit hyperactivity disorders, bipolar and post-traumatic stress disorders, epilepsy, autism, schizophrenia and drug abuse. However, repeated aggression is insufficiently studied because there is a lack of adequate models in animals. The sensory contact model (SCM), widely used to study the effects of chronic social defeat stress, can also be used to investigate the effects of repeated aggression. Mice with repeated positive fighting experience in daily agonistic interactions in this model develop pronounced aggressiveness, anxiety and impulsivity, disturbances in motivated and cognitive behaviors, and impairments of sociability; they also demonstrate hyperactivity, attention-deficit behavior, motor dysfunctions and repetitive stereotyped behaviors, such as jerks, rotations and head twitches. In this protocol, we describe how to apply the SCM to study repeated aggression in mice. Severe neuropathology develops in male mice after 20–21 d of agonistic interactions.

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Figure 1: Experimental cage.
Figure 2: Experimental design of the SCM for studying the effects of repeated agonistic interactions in male mice after 10 (10-d winners or 10-d losers) and 20 (20-d winners or 20-d losers) tests (d).
Figure 3: Significant correlations between parameters of the partition behavior of 10-d winners before agonistic interaction and parameters of agonistic behaviors after the partition is removed.
Figure 4: Total time spent near the partition as a reaction to the familiar partner in the neighboring compartment of common cage during the 5 min before agonistic interactions in mice of CBA/Lac and C57BL/6J strains.

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Acknowledgements

This research was supported by the Russian Scientific Foundation, grant no. 14-15-00063.

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Authors and Affiliations

  1. Siberian Department of Russian Academy of Sciences (SD RAS), Modeling of Neuropathologies Laboratory, Institute of Cytology and Genetics, Novosibirsk, Russia

    Natalia N Kudryavtseva, Dmitry A Smagin, Irina L Kovalenko & Galina B Vishnivetskaya

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  1. Natalia N Kudryavtseva
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  2. Dmitry A Smagin
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  3. Irina L Kovalenko
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Contributions

N.N.K. is an author of the SCM, oversaw the implementation of the overall projects concerning the study of repeated experience of aggression and defeats, carried out design of experiments and wrote the paper. N.N.K., D.A.S., I.L.K. and G.B.V. conducted the behavioral experiments and presented video files illustrating pathological behaviors.

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Correspondence to Natalia N Kudryavtseva.

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Supplementary information

Behavior of the C57BL/6J 20 d winners during the period of 5 min activation before agonistic interactions.

Winners demonstrate strong aggressive motivation (left compartment of the cage) as a reaction to the group-housed partner (right compartment of the cage). The group-housed partner is attempting to come to the partition. After partition removal the winner immediately attacks the partner. (MOV 3350 kb)

Behavior of the C57BL/6J 20 d winners during the period of 5 min activation before agonistic interactions.

Winners demonstrate strong aggressive motivation as a reaction to the 20 d. The loser does not approach the partition at all. After partition removal the winner immediately attacks the partner. There is a strong positive correlation between the total time spent near the partition as a reaction to the partner and the total attacking time or hostile behavior time during confrontation. (MOV 6717 kb)

Behavior of the DBA/2J 20 d winners (left compartment of the cage) during the period of 5 min activation before agonistic interactions with 20 d losers (right compartment).

The winners display chaotic movements in the cage without any attention to the partner in the next compartment of the cage. This behavior can be regarded as attention/deficit hyperactivity. There is no correlation between the total time spent near the partition as reaction to the partner and the total attacking time during the confrontation36. (MOV 5574 kb)

Behavior of the CBA/Lac 20 d winners during the period of 5 min activation before agonistic interactions (lower compartments of the cage) with 20 d losers (upper compartment).

All winners spent much time near the partition reacting to the losers. The winner in the left cage demonstrates stereotypic behaviors - turns around the axis of the body. (MOV 3565 kb)

Behavior of the C57BL/6J 20 d winner in unfamiliar cage. A group-housed male is used as a partner.

The winner demonstrates unusual repetitive backward movements. (MOV 3064 kb)

Jerks, head shakes, jumps, rotations, and hyperactivity demonstrated by the DBA/2J 20 d winners in agonistic interactions with 20 d losers.

The appearance of a large number of hyperkinetic movements manifested mostly in the form of sudden involuntary head movements (jerks), jumps with a turn were observed in the behavior of aggressive males during agonistic interactions36. (MOV 1229 kb)

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Kudryavtseva, N., Smagin, D., Kovalenko, I. et al. Repeated positive fighting experience in male inbred mice. Nat Protoc 9, 2705–2717 (2014). https://doi.org/10.1038/nprot.2014.156

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