title: The co-occurrence of zinc deficiency and social isolation has the opposite effects on mood compared with either condition alone due to changes in the central norepinephrine system.
abstract: Nutritional and social environmental problems during the early stages of life are closely associated with the pathophysiology of mood disorders such as depression. Disruption or dysfunction of the central norepinephrine (NE) system is also considered to play a role in mood disorders. Therefore, we evaluated the effects of zinc deficiency and/or social isolation on mood and changes in the central NE system using rats. Compared with the controls, the rats subjected to zinc deficiency or social isolation alone exhibited increased anxiety-related behavior in the elevated plus maze and greater depression-like behavior in the forced swim test. However, the co-occurrence of zinc deficiency and social isolation resulted in decreased anxiety-related behavior and control levels of depression-like behavior. Social isolation alone decreased the rats' cerebral NE concentrations. The expression of the NE transporter was not affected by social isolation alone, but its expression in the locus coeruleus was markedly decreased by the co-occurrence of social isolation and zinc deficiency, and this change was accompanied by an increase in the blood concentration of 3-methoxy-4-hydroxyphenylglycol, which is a marker of central NE system activity. These findings suggest that zinc deficiency or social isolation alone induce anxious or depressive symptoms, but the presence of both conditions has anxiolytic or antidepressive effects. Furthermore, these opposing effects of mood-related behaviors were found to be associated with changes in the central NE system.
authors: Department of Neuropsychiatry, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan.
authors: Hironori
authors: H
authors: Mitsuya
authors: Department of Neuropsychiatry, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan. Electronic address: omata@u-fukui.ac.jp.
authors: Naoto
authors: N
authors: Omata
authors: Biomedical Imaging Research Center, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan; Research and Education Program for Life Science, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan.
authors: Yasushi
authors: Y
authors: Kiyono
authors: Department of Neuropsychiatry, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan; Psychiatric Medical Center, Fukui Prefectural Hospital, 2-8-1 Yotsui, Fukui, Fukui 910-8526, Japan.
authors: Tomoyuki
authors: T
authors: Mizuno
authors: Department of Neuropsychiatry, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan; Psychiatric Medical Center, Fukui Prefectural Hospital, 2-8-1 Yotsui, Fukui, Fukui 910-8526, Japan.
authors: Tetsuhito
authors: T
authors: Murata
authors: Department of Neuropsychiatry, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan.
authors: Kayo
authors: K
authors: Mita
authors: Biomedical Imaging Research Center, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan.
authors: Hidehiko
authors: H
authors: Okazawa
authors: Department of Neuropsychiatry, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan.
authors: Yuji
authors: Y
authors: Wada
mesh_terms: D000339:Affect / Q000502:physiology*; D000821:Animal Feed; D000818:Animals; D001007:Anxiety / Q000378:metabolism; D001345:Autoradiography; D001835:Body Weight; D001921:Brain / Q000378:metabolism*; D003863:Depression / Q000378:metabolism; D005106:Exploratory Behavior / Q000502:physiology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism*; D017208:Rats, Wistar; D012934:Social Isolation / Q000523:psychology*; D015032:Zinc / Q000097:blood / Q000172:deficiency*
chemical_list: D050484:Norepinephrine Plasma Membrane Transport Proteins; C493226:Slc6a2 protein, rat; D015032:Zinc; D009638:Norepinephrine
keywords: Cerebral norepinephrine concentration; Elevated plus maze test; Forced swim test; Norepinephrine transporter; Social isolation; Zinc deficiency