title: Distribution of Fos-immunoreactive cells in rat forebrain and midbrain following social defeat stress and diazepam treatment.
abstract: The anxiolytic diazepam selectively inhibits psychological stress-induced autonomic and behavioral responses without causing noticeable suppression of other central performances. This pharmacological property of diazepam led us to the idea that neurons that exhibit diazepam-sensitive, psychological stress-induced activation are potentially those recruited for stress responses. To obtain neuroanatomical clues for the central stress circuitries, we examined the effects of diazepam on psychological stress-induced neuronal activation in broad brain regions. Rats were exposed to a social defeat stress, which caused an abrupt increase in body temperature by up to 2°C. Pretreatment with diazepam (4mg/kg, i.p.) attenuated the stress-induced hyperthermia, confirming an inhibitory physiological effect of diazepam on the autonomic stress response. Subsequently, the distribution of cells expressing Fos, a marker of neuronal activation, was examined in 113 forebrain and midbrain regions of these rats after the stress exposure and diazepam treatment. The stress following vehicle treatment markedly increased Fos-immunoreactive (IR) cells in most regions of the cerebral cortex, limbic system, thalamus, hypothalamus and midbrain, which included parts of the autonomic, neuroendocrine, emotional and arousal systems. The diazepam treatment significantly reduced the stress-induced Fos expression in many brain regions including the prefrontal, sensory and motor cortices, septum, medial amygdaloid nucleus, medial and lateral preoptic areas, parvicellular paraventricular hypothalamic nucleus, dorsomedial hypothalamus, perifornical nucleus, tuberomammillary nucleus, association, midline and intralaminar thalami, and median and dorsal raphe nuclei. In contrast, diazepam increased Fos-IR cells in the central amygdaloid nucleus, medial habenular nucleus, ventromedial hypothalamic nucleus and magnocellular lateral hypothalamus. These results provide important information for elucidating the neural circuitries that mediate the autonomic and behavioral responses to psychosocial stressors.
authors.affiliation: Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: B
authors.initials: B
authors.lastname: Lkhagvasuren
authors.affiliation: Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Oka
authors.affiliation: Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Division of Psychosomatic Medicine, Department of Neurology, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahata-Nishi-ku, Kitakyushu, Fukuoka 807-8555, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Sudo
authors.affiliation: Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan; Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, 4-1-8, Honcho, Kawaguchi, Saitama 332-0012, Japan. Electronic address: nkazuhir@gmail.com.
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000378:metabolism; D001522:Behavior, Animal; D003975:Diazepam / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D012919:Social Behavior; D013312:Stress, Physiological / Q000187:drug effects; D013315:Stress, Psychological / Q000188:drug therapy*
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D003975:Diazepam
keywords: emotion; mapping; psychogenic fever; psychological stress-induced hyperthermia; psychosocial stress; stress circuit