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Behavioral characterization of escalated aggression induced by GABAB receptor activation in the dorsal raphe nucleus

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Abstract

Rationale

Pharmacological activation of GABAB receptors in the dorsal raphe nucleus (DRN) can escalate territorial aggression in male mice.

Objectives

We characterized this escalated aggression in terms of its behavioral and environmental determinants.

Methods

Aggressive behavior of resident male (CFW or ICR mouse) was assessed in confrontations with a group-housed intruder. Either baclofen (0.06 nmol/0.2 μl) or vehicle (saline) was microinjected into the DRN 10 min before the confrontation. We examined baclofen-heightened aggression in five situations: aggression in a neutral arena and after social instigation (experiment 1), aggression during the light phase of the cycle (experiment 2), aggression without prior fighting experience (experiment 3), aggression toward a female (experiment 4), and aggression after defeat experiences (experiment 5). In addition, we examined the body targets towards which bites are directed and the duration of aggressive bursts after baclofen treatment.

Results

Regardless of the past social experience, baclofen escalated aggressive behaviors. Even in the neutral arena and after defeat experiences, where aggressive behaviors were inhibited, baclofen significantly increased aggression. Baclofen increased attack bites directed at vulnerable body areas of male intruders but not toward a female and only in the dark. Also, baclofen prolonged the duration of aggressive bursts.

Conclusions

For baclofen to escalate aggression, specific stimulation (male intruder) and tonic level of serotonin (dark cycle) are required. Once aggressive behavior is triggered, intra-DRN baclofen escalates the level of aggression to abnormal levels and renders it difficult to terminate. Also, baclofen counteracts the effects of novelty or past experiences of defeat.

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Acknowledgments

The authors would like to thank J Thomas Sopko for his outstanding technical assistance. This research was funded by NIAAA grant AA013983 (KAM) and by KAKENHI (22830130 and 23683021) and the Research Foundation for Opto-Science and Technology (AT).

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There is no conflict of interest in this paper.

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Correspondence to Aki Takahashi.

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Supplemental Fig. 1

Schematic representation of injection sites for experiments 1–5 in mouse coronal brain section (Paxinos and Franklin 2011). White circles indicate injection sites within the DRN, and black circles represent injection sites outside the DRN. In four cases in experiment 1, precise localization could not be confirmed due to technical problems (DOC 227 kb)

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Takahashi, A., Schilit, A.N., Kim, J. et al. Behavioral characterization of escalated aggression induced by GABAB receptor activation in the dorsal raphe nucleus. Psychopharmacology 224, 155–166 (2012). https://doi.org/10.1007/s00213-012-2654-8

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  • DOI: https://doi.org/10.1007/s00213-012-2654-8

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