Monosodium glutamate, a food additive, induces depressive-like and anxiogenic-like behaviors in young rats.

UNLABELLED Monosodium glutamate (MSG) has been the target of research due to its toxicological effects. AIMS We investigated the depressive- and anxiogenic-like behaviors in rats exposed to neonatal subcutaneous injection of MSG. The involvement of the serotonergic system, by measuring [(3)H] serotonin (5-HT) uptake in cerebral cortices, and the hypothalamic pituitary adrenal (HPA) axis, by determining serum adrenocorticotropic hormone (ACTH) and corticosterone levels, was also examined. MATERIALS AND METHODS Male and female newborn Wistar rats were divided into control and MSG groups, which received, respectively, a daily subcutaneous injection of saline (0.9%) or MSG (4 g/kg/day) from the 1st to 5th postnatal day. The behavioral tests [spontaneous locomotor activity, contextual fear conditioning, and forced swimming test (FST)] were performed from the 60th to 64th postnatal day. MSG-treated animals showed alteration in the spontaneous locomotor activity, an increase in the number of fecal pellets and the number of animal's vocalizations and urine occurrence, and a decrease in the grooming time. KEY FINDINGS The MSG exposure increased the immobility time in the FST and the freezing reaction in the contextual fear conditioning. Additionally, MSG treatment increased the [(3)H]5-HT uptake in the cerebral cortices of rats and induced a deregulation of HPA axis function (by increasing serum ACTH and corticosterone levels). SIGNIFICANCE In conclusion MSG-treated rats are more susceptible to develop anxiogenic- and depressive-like behaviors, which could be related to a dysfunction in the serotonergic system.

[1]  Y. Magami,et al.  Turnover of acinar and islet cells in the pancreas of monosodium glutamate-treated obese mice. , 2003, Obesity research.

[2]  A. Morales-Villagrán,et al.  Monosodium glutamate neonatal treatment as a seizure and excitotoxic model , 2010, Brain Research.

[3]  C. M. Galhardi,et al.  Basic nutritional investigation Monosodium glutamate in standard and high-fiber diets: metabolic syndrome and oxidative stress in rats , 2005 .

[4]  R. Porsolt,et al.  Immobility induced by forced swimming in rats: effects of agents which modify central catecholamine and serotonin activity. , 1979, European journal of pharmacology.

[5]  A. Boschero,et al.  Taurine prevents fat deposition and ameliorates plasma lipid profile in monosodium glutamate-obese rats , 2011, Amino Acids.

[6]  O. A. Rotimi,et al.  Effects of fibre-enriched diets on tissue lipid profiles of MSG obese rats. , 2012, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[7]  C. M. Galhardi,et al.  Monosodium glutamate in standard and high-fiber diets: metabolic syndrome and oxidative stress in rats. , 2005, Nutrition.

[8]  C. Nemeroff,et al.  Neurotoxic amino acids and structurally related analogs. , 1977, Pharmacological reviews.

[9]  Z. Hliňák,et al.  Behavioral deficits in adult rats treated neonatally with glutamate. , 2005, Neurotoxicology and teratology.

[10]  Z. Horváth,et al.  Changes in open-field activity and novelty-seeking behavior in periadolescent rats neonatally treated with monosodium glutamate , 2007, Neurotoxicity Research.

[11]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[12]  G. N. Babu,et al.  Lipid peroxidation potential and antioxidant status of circumventricular organs of rat brain following neonatal monosodium glutamate. , 1994, Neurotoxicology.

[13]  J. Olney.  GLUTAMATE‐INDUCED NEURONAL NECROSIS IN THE INFANT MOUSE HYPOTHALAMUS: An Electron Microscopic Study , 1971, Journal of neuropathology and experimental neurology.

[14]  D. Choi,et al.  Glutamate receptors and the induction of excitotoxic neuronal death. , 1994, Progress in brain research.

[15]  Š. Zórad,et al.  Late effects of postnatal administration of monosodium glutamate on insulin action in adult rats. , 2000, Physiological research.

[16]  W. Kostowski.  Possible relationship of the locus coeruleus--hippocampal noradrenergic neurons to depression and mode of action of antidepressant drugs. , 1985, Polish journal of pharmacology and pharmacy.

[17]  S. Zhan,et al.  Temporal and spatial expression of preprotachykinin A mRNA in the developing filial mice brain after maternal administration of monosodium glutamate at a late stage of pregnancy , 2007, Neuroscience.

[18]  F. F. Rocha,et al.  Antidepressant-like effect of Cecropia glazioui Sneth and its constituents - in vivo and in vitro characterization of the underlying mechanism. , 2007, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[19]  Daniel Hoyer,et al.  Molecular, pharmacological and functional diversity of 5-HT receptors , 2002, Pharmacology Biochemistry and Behavior.

[20]  P. Mathias,et al.  Vagotomy reduces obesity in MSG-treated rats. , 2000, Research communications in molecular pathology and pharmacology.

[21]  T. Frodl,et al.  How does the brain deal with cumulative stress? A review with focus on developmental stress, HPA axis function and hippocampal structure in humans , 2013, Neurobiology of Disease.

[22]  F. Antoni.  Vasopressinergic Control of Pituitary Adrenocorticotropin Secretion Comes of Age , 1993, Frontiers in Neuroendocrinology.

[23]  C. Phelix,et al.  Systemic glutamate induces degeneration of a subpopulation of serotonin-immunoreactive neurons in the area postrema of rats , 1990, Neuroscience Letters.

[24]  V. P. Whittaker,et al.  The isolation of nerve endings from brain: an electron-microscopic study of cell fragments derived by homogenization and centrifugation. , 1962, Journal of anatomy.

[25]  H. Westenberg,et al.  Anxiety disorders: a review of tricyclic antidepressants and selective serotonin reuptake inhibitors , 2000, Acta psychiatrica Scandinavica. Supplementum.

[26]  D. Nutt,et al.  The psychobiology of anxiolytic drug. Part 2: Pharmacological treatments of anxiety. , 2000, Pharmacology & therapeutics.

[27]  P. J. Larsen,et al.  Neonatal monosodium glutamate treatment alters both the activity and the sensitivity of the rat hypothalamo-pituitary-adrenocortical axis. , 1994, The Journal of endocrinology.

[28]  R. Bolles,et al.  Conditioned fear assessed by freezing and by the suppression of three different baselines , 1980 .

[29]  E. V. van Rossum,et al.  Glucocorticoid Receptor Polymorphisms in Major Depression , 2009, Annals of the New York Academy of Sciences.

[30]  M. Wong,et al.  Research and treatment approaches to depression , 2001, Nature Reviews Neuroscience.

[31]  Gilberto F. Xavier,et al.  Contextual, but not auditory, fear conditioning is disrupted by neurotoxic selective lesion of the basal nucleus of amygdala in rats , 2010, Neurobiology of Learning and Memory.

[32]  Sylvain Houle,et al.  Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression. , 2006, Archives of general psychiatry.

[33]  G. Chrousos,et al.  The endocrinology of melancholic and atypical depression: relation to neurocircuitry and somatic consequences. , 1999, Proceedings of the Association of American Physicians.

[34]  J. Olney.  Brain Lesions, Obesity, and Other Disturbances in Mice Treated with Monosodium Glutamate , 1969, Science.

[35]  J. Herman,et al.  Stress regulation of adrenocorticosteroid receptor gene transcription and mRNA expression in rat hippocampus: time-course analysis. , 2000, Brain research. Molecular brain research.

[36]  C. Pariante,et al.  Glucocorticoids, cytokines and brain abnormalities in depression , 2011, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[37]  Jiang-Ning Zhou,et al.  Imbalance of leptin pathway and hypothalamus synaptic plasticity markers are associated with stress-induced depression in rats , 2013, Behavioural Brain Research.

[38]  S. Asai,et al.  Hippocampal degeneration inducing impairment of learning in rats: model of dementia? , 1997, Behavioural Brain Research.

[39]  A. Brodish,et al.  Effects of chronic stress on in vivo pituitary-adrenocortical responses to corticotropin releasing hormone , 1990, Neuropeptides.

[40]  B. Hammock,et al.  Monosodium glutamate (MSG) intake is associated with the prevalence of metabolic syndrome in a rural Thai population , 2012, Nutrition & Metabolism.

[41]  P. Lelkes,et al.  Adrenal medullary function and expression of catecholamine-synthesizing enzymes in mice with hypothalamic obesity. , 2004, Life sciences.

[42]  P. Mathias,et al.  Fat storage is partially dependent on vagal activity and insulin secretion of hypothalamic obese rat , 2007, Endocrine.