Oral Monosodium Glutamate Differentially Affects Open-Field Behaviours, Behavioural Despair and Place Preference in Male and Female Mice

Author(s): Onaolapo AY, Olawore OI, Yusuf FO, Adeyemo AM, Adewole IO, Onaolapo OJ*.

Journal Name: Current Psychopharmacology

Volume 8 , Issue 2 , 2019

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Graphical Abstract:


Abstract:

Background: Monosodium glutamate (MSG) is a flavour enhancer which induces behavioural changes in animals. However the influence of sex on the behavioural response to MSG has not been investigated.

Objective: The sex-differential effects of MSG on open-field behaviours, anxiety-related behaviour, behavioural despair, place-preference, and plasma/brain glutamate levels in adult mice were assessed.

Methods: Mice were assigned to three groups (1-3), based on the models used to assess behaviours. Animals in group 1 were for the elevated-plus maze and tail-suspension paradigms, group 2 for the open-field and forced-swim paradigms, while mice in group 3 were for observation in the conditioned place preference paradigm. Mice in all groups were further assigned into five subgroups (10 males and 10 females), and administered vehicle (distilled water at 10 ml/kg) or one of four doses of MSG (20, 40, 80 and 160 mg/kg) daily for 6 weeks, following which they were exposed to the behavioural paradigms. At the end of the behavioural tests, the animals were sacrificed, and blood was taken for estimation of glutamate levels. The brains were also homogenised for estimation of glutamate levels.

Results: MSG was associated with a reduction in locomotion in males and females (except at 160 mg/kg, male), an anxiolytic response in females, an anxiogenic response in males, and decreased behavioural despair in both sexes (females more responsive). Postconditioning MSG-associated place-preference was significantly higher in females. Plasma/ brain glutamate was not significantly different between sexes.

Conclusion: Repeated MSG administration alters a range of behaviours in a sex-dependent manner in mice.

Keywords: Anxiolytic, central inhibition, depression, glutamate, sex, stereotypy.

[1]
Lovejoy JC, Sainsbury A. Stock conference 2008 working group sex differences in obesity and the regulation of energy homeostasis. Obes Rev 2009; 10: 154-67.
[2]
Counts SE, Che S, Ginsberg SD, Mufson EJ. Gender differences in neurotrophin and glutamate receptor expression in cholinergic nucleus basalis neurons during the progression of Alzheimer’s disease. J Chem Neuroanat 2011; 42: 111-7.
[3]
Gray AL, Hyde TM, Deep-Soboslay A, Kleinman JE, Sodhi MS. Sex differences in glutamate receptor gene expression in major depression and suicide. Mol Psychiatry 2015; 20: 1057-68.
[4]
Freeman E, Lin J, Chow S, Davis C, Li M. Sex differences in aripiprazole sensitization from adolescence to adulthood. Pharmacol Biochem Behav 2017; 156: 39-47.
[5]
Link JC, Reue K. Genetic basis for sex differences in obesity and lipid metabolism. Annu Rev Nutr 2017; 37: 225-45.
[6]
Tronieri JS, Wurst CM, Pearl RL, Allison KC. Sex differences in obesity and mental health. Curr Psychiatry Rep 2017; 19: 29.
[7]
Gale EA, Gillespie KM. Diabetes and gender. Diabetologia 2001; 44: 3-15.
[8]
Umpierrez GE, Smiley D, Kitabchi AE. Narrative review: ketosis-prone type 2 diabetes mellitus. Ann Intern Med 2006; 144: 350-7.
[9]
Werling DM, Geschwind DH. Sex differences in autism spectrum disorders. Curr Opin Neurol 2013; 26: 146-53.
[10]
Comitato R, Saba A, Turrini A, Arganini C, Virgili F. Sex hormones and macronutrient metabolism. Crit Rev Food Sci Nutr 2015; 55: 227-41.
[11]
Bristow GC, Bostrom JA, Haroutunian V, Sodhi MS. Sex differences in GABAergic gene expression occur in the anterior cingulate cortex in schizophrenia. Schizophr Res 2015; 167: 57-63.
[12]
Wickens MM, Bangasser DA, Briand LA. Sex differences in psychiatric disease: a focus on the glutamate system. Front Mol Neurosc 2018; 11: 197.
[13]
Stover JF, Kempski OS. Anesthesia increases circulating glutamate in neurosurgical patients. Acta Neurochir 2005; 147: 847-53.
[14]
Sailasuta N, Ernst T, Chang L. Regional variations and the effects of age and gender on glutamate concentrations in the human brain. Magn Reson Imaging 2008; 26: 667-75.
[15]
Teichberg VI, Cohen-Kashi-Malina K, Cooper I, Zlotnik A. Homeostasis of glutamate in brain fluids: an accelerated brain-to-blood efflux of excess glutamate is produced by blood glutamate scavenging and offers protection from neuropathologies. Neuroscience 2009; 158: 301-8.
[16]
Grachev ID, Apkarian AV. Chemical heterogeneity of the living human brain: a proton MR spectroscopy study on the effects of sex, age, and brain region. Neuroimage 2000; 11: 554-63.
[17]
Zahr NM, Mayer D, Rohlfing T, et al. In vivo glutamate measured with magnetic resonance spectroscopy: behavioral correlates in aging. Neurobiol Aging 2013; 34: 1265-76.
[18]
Frankfurt M, Fuchs E, Wuttke W. Sex differences in gamma-aminobutyric acid and glutamate concentrations in discrete rat brain nuclei. Neurosci Lett 1984; 50: 245-50.
[19]
Monfort P, Gomez-Gimenez B, Llansola M, Felipo V. Gender differences in spatial learning, synaptic activity, and long-term potentiation in the hippocampus in rats: molecular mechanisms. ACS Chem Neurosci 2015; 6: 1420-7.
[20]
McCabe C, Rolls ET. Umami: a delicious flavour formed by convergence of taste and olfactory pathways in the human brain. European J Neurosci 2007; 25: 1855-64.
[21]
Onaolapo OJ, Onaolapo AY. Acute low dose monosodium glutamate retards novelty induced behaviours in male Swiss albino mice. J Neurosci Behav Health 2011; 3: 51-6.
[22]
Onaolapo OJ, Onaolapo AY, Akanmu MA, Olayiwola G. Foraging enrichment modulates open field response to monosodium glutamate in mice. Ann Neurosci 2015; 22: 162-70.
[23]
Onaolapo OJ, Onaolapo AY, Akanmu MA, Gbola O. Evidence of alterations in brain structure and antioxidant status following ‘low-dose’ monosodium glutamate ingestion. Pathophysiology 2016; 23: 147-56.
[24]
Onaolapo OJ, Onaolapo AY, Akanmu MA, Olayiwola G. Changes in Spontaneous working-memory, memory-recall and approach-avoidance following “low dose” monosodium glutamate in mice. AIMS Neuroscience 2016; 3: 317-37.
[25]
Onaolapo OJ, Aremu OS, Onaolapo AY. Monosodium glutamate-associated alterations in open field, anxiety-related and conditioned place preference behaviours in mice. Naunyn Schmiedebergs Arch Pharmacol 2017; 390: 677-89.
[26]
Larsen PJ, Mikkelsen JD, Jessop D, Lightman SL, Chowdrey HS. Neonatal monosodium glutamate treatment alters both the activity and the sensitivity of the rat hypothalamo-pituitary-adrenocortical axis. J Endocrinol 1994; 141: 497-503.
[27]
Seo HJ, Ham H-D, Jin HY, et al. Chronic administration of monosodium glutamate under chronic variable stress impaired hypothalamic-pituitary-adrenal axis function in rats. Korean J Physiol Pharmacol 2010; 14: 213-21.
[28]
Dief AE, Kamha ES, Baraka AM, Elshorbagy AK. Monosodium glutamate neurotoxicity increases beta amyloid in the rat hippocampus: a potential role for cyclic AMP protein kinase. NeuroToxicol 2014; 42: 76-82.
[29]
Lima CB, Soares GSF, Vitor SM, et al. Neonatal treatment with monosodium glutamate lastingly facilitates spreading depression in the rat cortex. Life Sciences 2013; 93: 388-92.
[30]
Gudiño-Cabrera G, Ureña-Guerrero ME, Rivera-Cervantes MC, Feria-Velasco AI, Beas-Zárate C. Excitotoxicity triggered by neonatal monosodium glutamate treatment and blood-brain barrier function. Arch Med Res 2014; 45: 653-9.
[31]
Sagae SC, Grassiolli S, Raineki C, Balbo SL, Marques da Silva AC. Sex differences in brain cholinergic activity in MSG-obese rats submitted to exercise. Can J Physiol Pharmacol 2011; 89: 845-53.
[32]
Hawkins RA. The blood-brain barrier and glutamate. Am J Clin Nutr 2009; 90: 867S-74S.
[33]
Kondoh T, Mallick HN, Torii K. Activation of the gut-brain axis by dietary glutamate and physiologic significance in energy homeostasis. Am J Clin Nutr 2009; 90: 832S-7S.
[34]
Quines CB, Rosa SG, Da Rocha JT, et al. Monosodium glutamate, a food additive, induces depressive-like and anxiogenic-like behaviors in young rats. Life Sci 2-14 107: 27-31.
[35]
Rosa SG, Quines CB, Stangherlin EC, Nogueira CW. Diphenyl diselenide ameliorates monosodium glutamate induced anxiety-like behavior in rats by modulating hippocampal BDNF-Akt pathway and uptake of GABA and serotonin neurotransmitters. Physiol Behav 2016; 155: 1-8.
[36]
Vitor-de-Lima SM, Medeiros LB, Benevides RDL, Dos Santos CN, Lima da Silva NO, Guedes RCA. Monosodium glutamate and treadmill exercise: anxiety-like behavior and spreading depression features in young adult rats. Nutr Neurosci 2017; 10: 1-9.
[37]
Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 1985; 85: 367-70.
[38]
Młyniec K, Nowak G. Zinc deficiency induces behavioral alterations in the tail suspension test in mice. Effect of antidepressants. Pharmacol Rep 2012; 64: 249-55.
[39]
Porsolt RD, Bertin A, Jalfre M. Behavioural despair in mice: A primary screening test for antidepressants. Arch Int Pharmacodyn Ther 1997; 229: 327-36.
[40]
Kroczka B, Branski P, Palucha A, Pilc A, Nowak G. Antidepressant-like properties of zinc in rodent forced swim test. Brain Res Bull 2001; 55: 297-300.
[41]
Schechter MD, Calcagnetti DJ. Trends in place preference conditioning with a cross-indexed bibliography: 1957-1991. Neurosci Biobehav Rev 1993; 17: 21-41.
[42]
Carrier N, Wang X, Sun L, Lu XY. Sex-Specific and estrous cycle-dependent antidepressant-like effects and hippocampal akt signaling of leptin. Endocrinology 2015; 156: 3695-705.
[43]
Nelson RJ. An introduction to behavioral endocrinology. Sunderland: Sinauer Associates 2005.
[44]
Padilla E, Barrett D, Shumake J, Gonzalez-Lima F. Strain, sex, and open-field behavior: factors underlying the genetic susceptibility to helplessness. Behav Brain Res 2009; 201: 257-64.
[45]
Byers SL, Wiles MV, Dunn SL, Taft RA. Mouse estrous cycle identification tool and images. PLoS One 2012; 7e35538
[46]
Shi H, Clegg DJ. Sex differences in the regulation of body weight. Physiol Behav 2009; 97: 199-204.
[47]
Rudyk MP, Pozur VV, Voieikova DO, et al. Sex-based differences in phagocyte metabolic profile in rats with monosodium glutamate-induced obesity. Sci Rep 2018; 8: 5419.
[48]
Schneeberger M, Tan K, Nectow AR, et al. Friedman JM. Functional analysis reveals differential effects of glutamate and MCH neuropeptide in MCH neurons. Mol Metab 2018; 13: 83-9.
[49]
Xu Y, Wu Z, Sun H, et al. Glutamate mediates the function of melanocortin receptor 4 on Sim1 neurons in body weight regulation. Cell Metab 2013; 18: 860-70.
[50]
Delgado TC. Glutamate and GABA in appetite regulation. Front Endocrinol 2013; 4: 103.
[51]
Ploj K, Albery-Larsdotter S, Arlbrandt S, Kjaer MB, Skantze PM, Storlien LH. The metabotropic glutamate mGluR5 receptor agonist CHPG stimulates food intake. Neuroreport 2010; 21: 704-8.
[52]
Kondoh T, Torii K. MSG intake suppresses weight gain, fat deposition, and plasma leptin levels in male Sprague-Dawley rats. Physiol Behav 2008; 95: 135-44.
[53]
Smith QR. Transport of glutamate and other amino acids at the blood-brain barrier. J Nutr 2000; 130: 1016S-22S.
[54]
Zlotnik A, Ohayon S, Gruenbaum BF, et al. VI Determination of factors affecting glutamate concentrations in the whole blood of healthy human volunteers. J Neurosurg Anesthesiol 2011; 23: 45-9.
[55]
Onaolapo OJ, Onaolapo AY, Mosaku TJ, Onigbinde OA, Oyedele RA. Elevated plus maze and Y-maze behavioral effects of subchronic, oral low dose monosodium glutamate in Swiss albino mice. IOSR-JPBS 2012; 3: 21-7.
[56]
Rodgers RJ, Cole JC. Influence of social isolation, gender, strain, and prior novelty on plus-maze behaviour in mice. Physiol Behav 1993; 54: 729-36.
[57]
Võikar V, Kõks S, Vasar E, Rauvala H. Strain and gender differences in the behavior of mouse lines commonly used in transgenic studies. Physiol Behav 2001; 72: 271-81.
[58]
Nutt DJ, Ballenger JC, Sheehan D, Wittchen HU. Generalized anxiety disorder: comorbidity, comparative biology and treatment. J Neuropsychopharmacol 2002; 5: 315-25.
[59]
Wierońska JM, Stachowicz K, Nowak G, Pilc A. The loss of glutamate-GABA harmony in anxiety disorders. IntechOpen: London 2011.
[60]
Cortese BM, Phan KL. The role of glutamate in anxiety and related disorders. CNS Spectr 2005; 10: 820-30.
[61]
Goldstein JM, Jerram M, Abbs B, Whitfield-Gabrieli S, Makris N. Sex differences in stress response circuitry activation dependent on female hormonal cycle. J Neurosci 2010; 30: 431-8.
[62]
Kogler L, Gur RC, Derntl B. Sex differences in cognitive regulation of psychosocial achievement stress: brain and behavior. Hum Brain Mapp 2015; 36: 1028-42.
[63]
Maeng LY, Milad MR. Sex differences in anxiety disorders: Interactions between fear, stress, and gonadal hormones. Horm Behav 2015; 76: 106-17.
[64]
Fernandes C, González MI, Wilson CA, File SE. Factor analysis shows that female rat behaviour is characterized primarily by activity, male rats are driven by sex and anxiety. Pharmacol Biochem Behav 1999; 64: 731-8.
[65]
Kiss P, Hauser D, Tamás A, et al. Changes in open-field activity and novelty-seeking behavior in periadolescent rats neonatally treated with monosodium glutamate. Neurotox Res 2007; 12: 85-93.
[66]
Pulvirenti L, Berrier R, Kreifeldt M, Koob GF. Modulation of locomotor activity by NMDA receptors in the nucleus accumbens core and shell regions of the rat. Brain Res 1994; 664: 231-6.
[67]
Onaolapo OJ, Onaolapo AY, Akanmu MA, Olayiwola G. Caffeine and sleep-deprivation mediated changes in open-field behaviours, stress response and antioxidant status in mice. Sleep Sci 2016; 9: 236-43. c
[68]
Dunn AJ, Webster EL, Nemeroff CB. Neonatal treatment with monosodium glutamate does not alter grooming behavior induced by novelty or adrenocorticotropic hormone. Behav Neural Biol 1985; 44: 80-9.
[69]
Adriani W, Laviola G. A unique hormonal and behavioral hyporesponsivity to both forced novelty and d-amphetamine in periadolescent mice. Neuropharmacol 2000; 39: 334-46.
[70]
Auger AP, Olesen KM. Sex differences and the organisation of juvenile social play behaviour. J Neuroendocrinol 2009; 21: 519-25.
[71]
Cox KH, Rissman EF. Sex differences in juvenile mouse social behavior are influenced by sex chromosomes and social context. Genes Brain Behav 2011; 10: 465-72.
[72]
To CT, Bagdy G. Anxiogenic effect of central CCK administration is attenuated by chronic fluoxetine or ipsapirone treatment. Neuropharmacology 1999; 38: 279-82.
[73]
Carey RJ, DePalma G, Damianopoulos E. Evidence for Pavlovian conditioning of cocaine-induced responses linked to emotional behavioral effects. Pharmacol Biochem Behav 205(80): 123-34.
[74]
Shopsin B. The clinical antidepressant effect of exogenous agmatine is not reversed by parachlorophenylalanine: a pilot study. Acta Neuropsychiatr 2013; 25: 113-8.
[75]
Wright DJ, Gray LJ, Finkelstein DI, et al. N-acetylcysteine modulates glutamatergic dysfunction and depressive behavior in Huntington’s disease. Human Mol Genetic 2016; 25: 2923-33.
[76]
Orsini C, Bonito-Oliva A, Conversi D, Cabib S. Susceptibility to conditioned place preference induced by addictive drugs in mice of the C57BL/6 and DBA/2 inbred strains. Psychopharmacol 2005; 181: 327-36.
[77]
Khan A, Brodhead AE, Schwartz KA, Kolts RL, Brown WA. Sex differences in antidepressant response in recent antidepressant clinical trials. J Clin Psychopharmacol 2005; 25: 318-24.
[78]
Belzung C, Barreau S. Differences in drug-induced place conditioning between BALB/c and C57Bl/6 mice. Pharmacol Biochem Behav 2000; 65: 419-23.
[79]
Becker JB, Hu M. Sex differences in drug abuse. Frontiers in Neuroendocrinol 2008; 29: 36-47.
[80]
Carroll ME, Anker JJ. Sex differences and ovarian hormones in animal models of drug dependence. Hormones and Behavior 2010; 58: 44-56.
[81]
Anker JJ, Carroll ME. Females are more vulnerable to drug abuse than males: evidence from preclinical studies and the role of ovarian hormones. Curr Topin Behav Neurosci 2011; 8: 73-96.
[82]
Siuciak JA, McCarthy SA, Chapin DS, Reed TM, Vorhees CV, Repaske DR. Behavioral and neurochemical characterization of mice deficient in the phosphodiesterase-1B (PDE1B) enzyme. Neuropharmacology 2007; 53: 113-24.
[83]
Tzschentke TM, Schmidt WJ. Glutamatergic mechanisms in addiction. Mol Psychiatry 2003; 8: 373-82.
[84]
Kawasaki Y, Jin C, Suemaru K, et al. Effect of glutamate receptor antagonists on place aversion induced by naloxone in single-dose morphine- treated rats. Br J Pharmacol 2005; 145: 751-7.
[85]
He Z, Chen Y, Dong H, Su R, Gong Z, Yan L. Inhibition of vesicular glutamate transporters contributes to attenuate methamphetamine-induced conditioned place preference in rats. Behav Brain Res 2014; 267: 1-5.
[86]
Hyman SE, Malenka RC. Addiction and the brain: the neurobiology of compulsion and its persistence. Nat Rev Neurosci 2001; 2: 695-703.
[87]
Thomas MJ, Kalivas PW, Shaham Y. Neuroplasticity in the mesolimbic dopamine system and cocaine addiction. British J Pharmacol 2008; 154: 327-42.
[88]
Groenewegen HJ, Wright CI, Beijer AV. The nucleus accumbens: gateway for limbic structures to reach the motor system? Progress Brain Res 1996; 107: 485-511.


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Article Details

VOLUME: 8
ISSUE: 2
Year: 2019
Page: [130 - 145]
Pages: 16
DOI: 10.2174/2211556008666181213160527

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