title: Glutamate input in the dorsal raphe nucleus as a determinant of escalated aggression in male mice.
abstract: Although 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.
authors.affiliation: 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.
authors.forename: Aki
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Mouse Genomics Resource Laboratory, National Institute of Genetics (NIG), Department of Life Science, National Taiwan University, Taipei, 10617 Taiwan, Okinawa Institute of Science and Technology Graduate University, Onna-son, Kunigami-gun, Okinawa, 904-0495 Japan.
authors.forename: Ray X
authors.initials: RX
authors.lastname: Lee
authors.affiliation: Department of Genetics, The Graduate University for Advanced Studies, and Division of Neurogenetics, NIG, Mishima, Shizuoka, 411-8540 Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Iwasato
authors.affiliation: Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Wako-shi, Saitama, 351-0198 Japan.
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550 Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arima
authors.affiliation: Department of Biomedicine, University of Basel, Basel CH-4056, Switzerland, and.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Bettler
authors.affiliation: Departments of Psychology, Neuroscience, Pharmacology, and Psychiatry, Tufts University, Medford, Massachusetts 02155.
authors.forename: Klaus A
authors.initials: KA
authors.lastname: Miczek
authors.affiliation: Mouse Genomics Resource Laboratory, National Institute of Genetics (NIG), Department of Genetics, The Graduate University for Advanced Studies, and.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Koide
mesh_terms: D000374:Aggression / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000494:pharmacology; D065847:Dorsal Raphe Nucleus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008845:Microinjections; D017397:Prefrontal Cortex / Q000378:metabolism; D018080:Receptors, GABA-B / Q000235:genetics; D059326:Serotonergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018080:Receptors, GABA-B; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D001418:Baclofen
keywords: GABAB receptor; dorsal raphe nucleus; escalated aggression; glutamate; serotonin (5-HT); species-typical aggressive behavior