Behavioral deficits in adult rats treated neonatally with glutamate.

The present study evaluated long-term behavioral consequences of neonatal monosodium-l-glutamate (MSG) treatment in rats. The pups received MSG (3 mg/g sc) daily from postnatal day (PD) 5-12. Data from an automatic activity monitor showed that locomotion of MSG-treated females and males aged 56 and 84 days was significantly reduced. Beginning PD 120, three behavioral tests were performed. As compared to the controls, in the elevated plus maze test, modified to evaluate the adaptive form of spatial memory, MSG-treated animals of both sex had significantly prolonged start and transfer latencies. In the social recognition test, assessing olfactory working memory, MSG-treated males displayed a reduced interest in the juvenile conspecific as the stimulus partner during both the initial exposure and re-exposure performed 30 min later. In the open field test, a significant decrease in the habituation rate was found in MSG-treated animals. Sex-dependent differences in behavioral performance were suggested in the open field and elevated plus maze tests. Behavioral changes are discussed in light of the deficits in perception and processing of visual and olfactory stimuli.

[1]  Thomas R. Insel,et al.  The Neuroendocrine Basis of Social Recognition , 2002, Frontiers in Neuroendocrinology.

[2]  J. Olney,et al.  Drug‐induced Apoptotic Neurodegeneration in the Developing Brain , 2002, Brain pathology.

[3]  B. Beck,et al.  Behavioral deficits in monosodium glutamate rats: specific changes in the structure of feeding behavior. , 1998, Life sciences.

[4]  P. L. Carlton,et al.  Pharmacological and anatomical dissociation of two types of habituation. , 1974, Journal of comparative and physiological psychology.

[5]  Z. Hliňák,et al.  N-Methyl-d-aspartate improved social recognition potency in rats , 2002, Neuroscience Letters.

[6]  H. Fibiger.  Cholinergic mechanisms in learning, memory and dementia: a review of recent evidence , 1991, Trends in Neurosciences.

[7]  D. Jezova,et al.  Changes of Exploratory Behaviour and Its Habituation in Rats Neonatally Treated with Monosodium Glutamate , 1997, Pharmacology Biochemistry and Behavior.

[8]  R. Dantzer,et al.  Centrally injected arginine vasopressin (AVP) facilitates social memory in rats , 1987, Neuroscience Letters.

[9]  S. Siegel,et al.  Nonparametric Statistics for the Behavioral Sciences , 2022, The SAGE Encyclopedia of Research Design.

[10]  C. Beas-Zárate,et al.  Neonatal exposure to monosodium glutamate induces cell death and dendritic hypotrophy in rat prefrontocortical pyramidal neurons , 2001, Neuroscience Letters.

[11]  J. Dobbing,et al.  Comparative aspects of the brain growth spurt. , 1979, Early human development.

[12]  J. Brankačk,et al.  Long-term effects on behaviour after postnatal treatment with monosodium-L-glutamate. , 1987, Biomedica biochimica acta.

[13]  D. Choi,et al.  Glutamate receptor-induced 45Ca2+ accumulation in cortical cell culture correlates with subsequent neuronal degeneration , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[14]  H. Tilson,et al.  Interlaboratory comparison of motor activity experiments: implications for neurotoxicological assessments. , 1991, Neurotoxicology and teratology.

[15]  J. Kleim,et al.  The postweaning housing environment determines expression of learning deficit associated with neonatal monosodium glutamate (M.S.G.). , 1991, Neurotoxicology and teratology.

[16]  C. Wotjak,et al.  Endogenous oxytocin is involved in short-term olfactory memory in female rats , 1998, Behavioural Brain Research.

[17]  A. Konnerth,et al.  Long-term potentiation and functional synapse induction in developing hippocampus , 1996, Nature.

[18]  Pradhan Sn,et al.  Behavioral changes in adult rats treated with monosodium glutamate in the neonatal stage. , 1972 .

[19]  R. Rodgers,et al.  Resistance of experientially-induced changes in murine plus-maze behaviour to altered retest conditions , 1997, Behavioural Brain Research.

[20]  R. Mistlberger,et al.  Neonatal monosodium glutamate alters circadian organization of feeding, food anticipatory activity and photic masking in the rat , 1999, Brain Research.

[21]  P. Popik,et al.  RECOGNITION CUE IN THE RAT'S SOCIAL MEMORY PARADIGM , 1991, Journal of basic and clinical physiology and pharmacology.

[22]  T. Kameyama,et al.  Utility of an elevated plus-maze for the evaluation of memory in mice: effects of nootropics, scopolamine and electroconvulsive shock , 1990, Psychopharmacology.

[23]  Z. Hliňák,et al.  Concurrent administration of subeffective doses of scopolamine and MK-801 produces a short-term amnesia for the elevated plus-maze in mice , 1998, Behavioural Brain Research.

[24]  S. File,et al.  Validation of open : closed arm entries in an elevated plus-maze as a measure of anxiety in the rat , 1985, Journal of Neuroscience Methods.

[25]  C. Vorhees,et al.  A developmental test battery for neurobehavioral toxicity in rats: a preliminary analysis using monosodium glutamate calcium carrageenan, and hydroxyurea. , 1979, Toxicology and applied pharmacology.

[26]  K. Fuxe,et al.  Long-term treatment with zimelidine leads to a reduction in 5-hydroxytryptamine neurotransmission within the central nervous system of the mouse and rat , 1981, Neuroscience Letters.

[27]  M. Ichimura,et al.  Behavioural studies in rats treated with monosodium l-glutamate during the early stages of life , 1979 .

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

[29]  E. Cavalheiro,et al.  Deficit in hippocampal long-term potentiation in monosodium glutamate-treated rats , 2002, Brain Research Bulletin.

[30]  S. Aamodt,et al.  Developmental Depression of Glutamate Neurotransmission by Chronic Low-Level Activation of NMDA Receptors , 2001, The Journal of Neuroscience.

[31]  R. Dantzer,et al.  Role of the vomeronasal system in vasopressinergic modulation of social recognition in rats , 1993, Brain Research.

[32]  R. Dantzer,et al.  Vasopressin involvement in antipyresis, social communication, and social recognition: a synthesis. , 1992, Critical reviews in neurobiology.

[33]  R. L. Brunner,et al.  The effect of monosodium glutamate on the early biochemical and behavioral development of the rat. , 1974, Developmental psychobiology.

[34]  P. Groves,et al.  Habituation: a dual-process theory. , 1970, Psychological review.

[35]  J. Preston,et al.  The entry of acidic amino acids into brain and CSF during development, using in situ perfusion in the rat. , 1995, Brain research. Developmental brain research.

[36]  J Lát,et al.  The analysis of habituation. , 1973, Acta neurobiologiae experimentalis.

[37]  R. Robertson,et al.  Regional effect of monosodium-L-glutamate on the superficial layers of superior colliculus in rat , 2004, Cell and Tissue Research.

[38]  Attention and habituation: Separation of specific components in development , 1987, Physiology & Behavior.

[39]  A. Schally,et al.  Effect of monosodium glutamate on some endocrine functions. , 1971, Neuroendocrinology.

[40]  Zdeněk Hliňáck.  Social Recognition in Ovariectomized and Estradiol-Treated Female Rats , 1993, Hormones and Behavior.

[41]  T. Dawson,et al.  Gases as biological messengers: nitric oxide and carbon monoxide in the brain , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[42]  C. Beas-Zárate,et al.  Effect of L-glutamate on cholinergic neurotransmission in various brain regions and during the development of rats, when administered perinatally , 1997, Neurochemistry International.

[43]  A. Blokland.  Acetylcholine: a neurotransmitter for learning and memory? , 1995, Brain Research Reviews.

[44]  H. Maaswinkel,et al.  Roles of the basolateral amygdala and hippocampus in social recognition in rats , 1996, Physiology & Behavior.

[45]  D. Jezova,et al.  Neonatal Stress Alters Habituation of Exploratory Behavior in Adult Male but not Female Rats , 1999, Pharmacology Biochemistry and Behavior.

[46]  J. Olney,et al.  Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. , 1999, Science.

[47]  A. Cools,et al.  Role of the nucleus accumbens in social memory in rats , 1991, Brain Research Bulletin.

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

[49]  Michael V. Johnston,et al.  Physiological and pathophysiological roles of excitatory amino acids during central nervous system development , 1990, Brain Research Reviews.

[50]  D. Lucas,et al.  The toxic effect of sodium L-glutamate on the inner layers of the retina. , 1957, A.M.A. archives of ophthalmology.

[51]  P. L. Carlton.  Brain acetylcholine and habituation. , 1968, Progress in brain research.

[52]  T. McCall,et al.  Nitric oxide takes centre-stage with newly defined roles. , 1992, Trends in pharmacological sciences.

[53]  W. Slikker,et al.  Ontogeny of the N-methyl-D-aspartate (NMDA) receptor system and susceptibility to neurotoxicity. , 2002, Toxicological sciences : an official journal of the Society of Toxicology.

[54]  I. Izquierdo,et al.  Neurotransmitter receptors involved in post-training memory processing by the amygdala, medial septum, and hippocampus of the rat. , 1992, Behavioral and neural biology.

[55]  H. Tilson,et al.  Neonatal exposure to monosodium glutamate alters the neurobehavioral performance of adult rats. , 1981, Neurotoxicology.

[56]  Johnston Mv,et al.  Excitatory amino acid neurotoxicity in the developing brain. , 1993 .

[57]  S. Morato,et al.  The role of vision and proprioception in the aversion of rats to the open arms of an elevated plus-maze , 2002, Behavioural Processes.

[58]  J. Olney.  THE TOXIC EFFECTS OF GLUTAMATE AND RELATED COMPOUNDS IN THE RETINA AND THE BRAIN , 1982, Retina.

[59]  J. Preston,et al.  Changes in the kinetics of the acidic amino acid brain and CSF uptake during development in the rat. , 1997, Brain research. Developmental brain research.

[60]  Y. Takasaki,et al.  Effects of parenteral and oral administration of monosodium l-glutamate (MSG) on somatic growth in rats , 1979 .

[61]  K. Edelstein,et al.  Neonatal monosodium glutamate treatment prevents effects of constant light on circadian temperature rhythms of adult rats , 1995, Brain Research.

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

[63]  T. Kameyama,et al.  Utility of an elevated plus-maze for dissociation of amnesic and behavioral effects of drugs in mice. , 1991, European journal of pharmacology.

[64]  D. Choi,et al.  Glutamate neurotoxicity and diseases of the nervous system , 1988, Neuron.

[65]  A. Sadile,et al.  Behavioral habituation to spatial novelty: Interference and noninterference studies , 1994, Neuroscience & Biobehavioral Reviews.

[66]  M. Wilkinson,et al.  Recovery of hypothalamic NMDA-induced c-fos expression following neonatal glutamate (MSG) lesions. , 1997, Brain research. Developmental brain research.

[67]  H. Hatt.  Modification of Glutamate Receptor Channels: Molecular Mechanisms and Functional Consequences , 1999, Naturwissenschaften.

[68]  D. H. Thor,et al.  Social memory of the male laboratory rat. , 1982 .

[69]  R. Dantzer,et al.  Modulation of social memory in male rats by neurohypophyseal peptides , 1987, Psychopharmacology.

[70]  C. A. Blake,et al.  Monosodium glutamate disruption of behavioral and endocrine function in the female rat. , 1980, Neuroendocrinology.

[71]  U. K. Misra,et al.  Locomotor and learning deficits in adult rats exposed to monosodium-l-glutamate during early life , 2000, Neuroscience Letters.

[72]  H. Maaswinkel,et al.  Executive function of the hippocampus in social behavior in the rat. , 1997, Behavioral neuroscience.

[73]  P A Salin,et al.  Dendritic glutamate autoreceptors modulate signal processing in rat mitral cells. , 2001, Journal of neurophysiology.

[74]  J. Viña,et al.  Penetration of Glutamate into Brain of 7-day-old Rats , 1997, Metabolic Brain Disease.