RT Journal Article
SR Electronic
T1 Glutamate Input in the Dorsal Raphe Nucleus As a Determinant of Escalated Aggression in Male Mice
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 6452
OP 6463
DO 10.1523/JNEUROSCI.2450-14.2015
VO 35
IS 16
A1 Aki Takahashi
A1 Ray X. Lee
A1 Takuji Iwasato
A1 Shigeyoshi Itohara
A1 Hiroshi Arima
A1 Bernhard Bettler
A1 Klaus A. Miczek
A1 Tsuyoshi Koide
YR 2015
UL http://www.jneurosci.org/content/35/16/6452.abstract
AB 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.