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Involvement of Catecholaminergic and Gabaaergic Mediations in the Anxiety-Related Behavior in Long-Term Powdered Diet-Fed Mice T

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Involvement of Catecholaminergic and Gabaaergic Mediations in the Anxiety-Related Behavior in Long-Term Powdered Diet-Fed Mice T Neurochemistry International 124 (2019) 1–9 Contents lists available at ScienceDirect Neurochemistry International journal homepage: www.elsevier.com/locate/neuint Involvement of catecholaminergic and GABAAergic mediations in the anxiety-related behavior in long-term powdered diet-fed mice T ∗ Fukie Yaoitaa, , Masahiro Tsuchiyab, Yuichiro Araic, Takeshi Tadanod, Koichi Tan-Noa a Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, 981-8558, Japan b Department of Nursing, Tohoku Fukushi University, 1-8-1 Kunimi, Aoba-ku, Sendai, 981-8522, Japan c Tokyo Ariake University of Medical and Health Science, 2-9-1 Ariake, Koto-Ku, Tokyo, 135-0063, Japan d Complementary and Alternative Medicine Clinical Research and Development, Graduate School of Medicine Sciences, Kanazawa University, Kakumamachi, Kanazawa, 920-1192, Japan ARTICLE INFO ABSTRACT Keywords: Dietary habits are important factors which affect metabolic homeostasis and the development of emotion. We Atomoxetine have previously shown that long-term powdered diet feeding in mice increases spontaneous locomotor activity Methylphenidate and social interaction (SI) time. Moreover, that diet causes changes in the dopaminergic system, especially PD168077 increased dopamine turnover and decreased dopamine D4 receptor signals in the frontal cortex. Although the Anxiety-related behavior increased SI time indicates low anxiety, the elevated plus maze (EPM) test shows anxiety-related behavior and Low anxiety impulsive behavior. In this study, we investigated whether the powdered diet feeding causes changes in anxiety- Bicuculline Attention deficit/hyperactivity disorder related behavior. Mice fed a powdered diet for 17 weeks from weaning were compared with mice fed a standard diet (control). The percentage (%) of open arm time and total number of arm entries were increased in powdered diet-fed mice in the EPM test. We also examined the effects of diazepam, benzodiazepine anti-anxiety drug, bicuculline, GABA-A receptor antagonist, methylphenidate, dopamine transporter (DAT) and noradrenaline transporter (NAT) inhibitor, atomoxetine, selective NAT inhibitor, GBR12909, selective DAT inhibitor, and PD168077, selective dopamine D4 receptor agonist, on the changes of the EPM in powdered diet-fed mice. Methylphenidate and atomoxetine are clinically used to treat attention deficit/hyperactivity disorder (ADHD) symptoms. The % of open arm time in powdered diet-fed mice was decreased by treatments of atomoxetine, methylphenidate and PD168077. Diazepam increased the % of open arm time in control diet-fed mice, but not in powdered diet-fed mice. The powdered diet feeding induced a decrease in GABA transaminase, GABA metabolic enzymes, in the frontal cortex. Moreover, the powdered diet feeding induced an increase in NAT expression, but not DAT expression, in the frontal cortex. These results suggest that the long-term powdered diet feeding may cause low anxiety or impulsivity, possibly via noradrenergic and/or dopaminergic, and GABAAergic mediations and increase the risk for onset of ADHD-like behaviors. 1. Introduction foods in part explain lesser developed masticatory function (Yamanaka et al., 2009). We recently reported that long-term powdered diet Various changes brought on by modern lifestyle have caused an feeding in mice increases spontaneous locomotor activity and social increased risk of disease. Dietary habits are particularly important interaction (SI) time of SI test. Moreover, this diet causes changes in the factors which affect development of the central nervous system as well dopaminergic system, in particular, increased dopamine turnover and as emotion (Aoki et al., 2005; Kushida et al., 2008; Mitome et al., 2005; decreased dopamine D4 receptor signals in the frontal cortex (Niijima- Niijima-Yaoita et al., 2013; Yamamoto and Hirayama, 2001). It has Yaoita et al., 2013). However, some reports suggest that the impairment been suggested that evolutionary changes in dietary habit to softer of dopaminergic activity in the hippocampus may be related to the Abbreviations: ADHD, attention deficit/hyperactivity disorder; ANOVA, analysis of variance; BZD, benzodiazepines; DAT, dopamine transporter; EPM, elevated plus maze; GABA-A, γ−amino butyric acid receptor type A; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; i.p., intraperitoneally; NA, noradrenaline; NAT, nor- adrenaline transporter; % of open arm time, percentage of time spent in the open arm; SI, social interaction; T-PBS, Tween-20 in phosphate-buffered saline ∗ Corresponding author. E-mail address: [email protected] (F. Yaoita). https://doi.org/10.1016/j.neuint.2018.12.002 Received 25 September 2018; Received in revised form 30 November 2018; Accepted 4 December 2018 Available online 07 December 2018 0197-0186/ © 2018 Elsevier Ltd. All rights reserved. F. Yaoita et al. Neurochemistry International 124 (2019) 1–9 masticatory dysfunction induced by powdered diet feeding (Kushida 2.2. Drugs and treatment et al., 2008; Yoshino et al., 2012). In addition to the SI test, the elevated plus maze (EPM) test is useful The following drugs were used: diazepam (Sigma–Aldrich, St. Louis, for evaluating anxiety-related behavior (File, 1992). It is known that MO, USA), bicuculline (GABA-A receptor antagonist, Tocris Bioscience, γ−amino butyric acid type A (GABA-A) receptor plays a critical role in Bristol, UK), methylphenidate (Novartis Pharma, Tokyo, Japan), ato- anxiolytic activity. GABA-A receptor is a chloride channel composed of moxetine (selective NET inhibitor, Sigma–Aldrich) and GBR12909 a pentameric hetero-oligometric protein with binding sites for GABA, (selective DAT inhibitor, Tocris Bioscience). Diazepam, bicuculline and benzodiazepines (BZD), barbiturates, and steroids, etc. The activation PD168077 (selective dopamine D4 receptor agonist, Sigma–Aldrich) of the GABA-A receptor induced by BZD including diazepam increases were suspended in saline containing 0.5% Tween 80. Methylphenidate, the percentage (%) of open arm time in the EPM test, indicating low atomoxetine and GBR12909 were dissolved in saline. All drugs were anxiety (i.e. anxiolytic effect) (for review see Jacob et al., 2008; Möhler administered intraperitoneally (i.p.) (volume: 0.1 ml/10 g body weight) et al., 2002). On the other hand, Hwang et al. (2004) reported that the at 30 min before the behavioral test. The drug doses used in the present increase in expression of GABA transaminase and GABA metabolic study were within the ranges widely used in experiments on mice and enzymes, provide important information about the brain with GABA rats (Gould et al., 2005; Hiraide et al., 2013; Kanegawa et al., 2010; dysfunction. Moreover, the GABA transaminase has been primarily in- Leggio et al., 2011; Niijima et al., 2006; Niijima-Yaoita et al., 2013; vestigated in relation to epilepsy, but it has also been found that a Robinson et al., 2012; Ueno et al., 2002). decrease in GABA neurotransmission appears to be involved in the aetiology of several neurological disorders such as anxiety (for review 2.3. EPM test see Kowalczyk and Kulig, 2014). Attention deficit/hyperactivity disorder (ADHD) is a neurodeve- At 20 weeks of age, the anxiety-related behavior was evaluated lopmental disorder characterized by inattention, hyperactivity, and using the EPM test. The apparatus consisted of two open arms impulsivity. Using the ADHD animal model, impulsive behavior can be (6 cm × 30 cm) opposite each other, crossed by two closed arms evaluated by the EPM test (Kishikawa et al., 2014; Niimi et al., 2011; (6 cm × 30 cm) (walls 10 cm) with an open roof and central platform Ueno et al., 2002). This test is designed to detect anxiety-related be- (9 cm × 9 cm). The maze floor and walls were constructed from acrylic havior but it also reflects impulsivity for novelty seeking. plate and elevated 40 cm from the ground floor. Initially, the animals The frontal cortex is an important brain region which is related to were placed on the central platform of the maze in front of a closed arm. ADHD symptoms, including impulsive behavior (for reviews see The animal had 5 min to explore the apparatus. Activity of mice was Arnsten and Pliszka, 2011; Brevet-Aeby et al., 2016; Herman et al., monitored via video camera positioned above the apparatus. The time 2018). The etiology and pathophysiology of ADHD have not been spent in each arm and the number of entries into each arm were au- completely clarified, however the prefrontal cortex is known to be tomatically analyzed offline using the ANY-maze video tracking soft- particularly sensitive to the neurochemical environment; relatively ware (Stoelting Company, Wood Dale, IL, USA). The test area was slight changes in the levels of noradrenaline (NA) and dopamine can cleaned with 20% ethanol between each session. produce significant changes in its function (for review see Arnsten and Pliszka, 2011). Although newer drugs have been developed, methyl- 2.4. Western blot analysis of GABA transaminase in the frontal cortex and phenidate and atomoxetine remain the predominantly prescribed drugs both NAT and DAT expressions in the frontal cortex and hippocampus for the treatment of ADHD. Methylphenidate increases extracellular dopamine and NA indirectly by blocking the transporters, dopamine After 17 weeks of treatment, animals were sacrificed by decaptation transporter (DAT) and NA transporter (NAT), while atomoxetine pre- without anesthesia. The brains were rapidly resected and two
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