• Aki Takahashi, Ray X Lee, Takuji Iwasato, Shigeyoshi Itohara, Hiroshi Arima, Bernhard Bettler, Klaus A Miczek, and Tsuyoshi Koide.
• Laboratory of Behavioral Neuroendocrinology, University of Tsukuba, Tsukuba, Ibaraki, 305-8577 Japan, Mouse Genomics Resource Laboratory, National Institute of Genetics (NIG), Department of Genetics, The Graduate University for Advanced Studies, and akitakahashi@kansei.tsukuba.ac.jp.
• J. Neurosci. 2015 Apr 22;35(16):6452-63.

AbstractAlthough the dorsal raphe nucleus (DRN) has long been linked to neural control of aggression, little is known about the regulatory influences of the DRN when an animal engages in either adaptive species-typical aggressive behavior or escalated aggression. Therefore it is important to explore which neurotransmitter inputs into the DRN determine the escalation of aggression in male mice. Previously, we observed that microinjection of the GABAB receptor agonist baclofen into the DRN escalates aggressive behavior in male mice. Here, we used a serotonin (5-HT) neuron-specific GABAB receptor knock-out mouse to demonstrate that baclofen acts on nonserotonergic neurons to escalate aggression. Intra-DRN baclofen administration increased glutamate release, but did not alter GABA release, within the DRN. Microinjection of l-glutamate into the DRN escalated dose-dependently attack bites toward an intruder. In vivo microdialysis showed that glutamate release increased in the DRN during an aggressive encounter, and the level of glutamate was further increased when the animal was engaged in escalated aggressive behavior after social instigation. Finally, 5-HT release was increased within the DRN and also in the medial prefrontal cortex when animals were provoked by social instigation, and during escalated aggression after social instigation, but this increase in 5-HT release was not observed when animals were engaged in species-typical aggression. In summary, glutamate input into the DRN is enhanced during escalated aggression, which causes a phasic increase of 5-HT release from the DRN 5-HT neurons.Copyright © 2015 the authors 0270-6474/15/356452-12$15.00/0.

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