title: Long-lasting effects of inescapable-predator stress on brain tryptophan metabolism and the behavior of juvenile mice.
abstract: The kynurenine (KYN) pathway, which is initiated by indoleamine 2,3-dioxygenase, is the main tryptophan (TRP) metabolic pathway. It shares TRP with the serotonin (5-HT) pathway. We investigated the influence of inescapable-predator (rat) stress on behavior and brain TRP metabolism in mice. Male ICR mice (4W) were exposed to 20-min inescapable-predator stress. Behavior on an elevated plus-maze, and TRP, KYN, and 5-HT levels in the prefrontal cortex, hippocampus, amygdala, and dorsal raphe nuclei were measured 1 and 4 weeks after stress exposure. Predator stress increased the number of open-arm entries (NOA) 4 weeks after stress exposure without altering the number of closed-arm entries (NCA). Thus, the open/closed-arm entry ratio (NOA/NCA) increased after stress exposure. Predator stress increased KYN levels in the prefrontal cortex (until 4 weeks after stress exposure) and dorsal raphe nuclei (for 1 week after stress exposure), decreased 5-HT levels in all brain regions (until 4 weeks after stress exposure). Thus, predator stress increased the KYN/5-HT ratio in all regions, in particular in the prefrontal cortex and hippocampus until 4 weeks after stress exposure. Predator stress shifted the balance between the KYN and 5-HT pathways to the KYN pathway, and induced behavioral disinhibition.
authors.affiliation: Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan. hmiura@med.nagoya-u.ac.jp
authors.forename: Hideki
authors.initials: H
authors.lastname: Miura
authors.forename: Yu
authors.initials: Y
authors.lastname: Ando
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Noda
authors.forename: Kenichi
authors.initials: K
authors.lastname: Isobe
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
mesh_terms: D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000378:metabolism; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D007737:Kynurenine / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017397:Prefrontal Cortex / Q000378:metabolism; D011903:Raphe Nuclei / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism*
chemical_list: D012701:Serotonin; D007737:Kynurenine; D014364:Tryptophan