The Origin and Neuronal Function of<i>In Vivo</i>Nonsynaptic Glutamate

Baker, David A.; Xi, Zheng‐Xiong; Shen, Hui; Swanson, Chad J.; Kalivas, Peter W.

doi:10.1523/jneurosci.22-20-09134.2002

Cited by 532 publications

(548 citation statements)

References 64 publications

(93 reference statements)

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“…In addition to the regulation of glutamate release, NAC, via GSH or its derivatives, has the capacity to modulate NMDA activity (Gilbert et al 1991;Leslie et al 1992;Varga et al 1997). NAC regulation of the cystine/glutamate antiporter and mGluR2/3, as described above, can also regulate dopamine release from presynaptic terminals (Baker et al 2002). NAC may also regulate dopamine release via the modulation of the redox status of the cell, via antioxidant effects of GSH and L-cysteine (JanÄky et al 2007; Gere-Paszti and Jakus 2009).…”

Section: Discussionmentioning

confidence: 97%

Behavioral Responses in Rats Submitted to Chronic Administration of Branched-Chain Amino Acids

et al. 2013

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Maple syrup urine disease (MSUD) is an inborn metabolism error caused by a deficiency of branched-chain a-keto acid dehydrogenase complex activity. This blockage leads to an accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine, and valine, as well as their corresponding a-keto and a-hydroxy acids. Previous reports suggest that MSUD patients are at high risk for chronic neuropsychiatric problems. Therefore, in this study, we assessed variables that suggest depressive-like symptoms (anhedonia as measured by sucrose intake, immobility during the forced swimming test and body and adrenal gland weight) in rats submitted to chronic administration of BCAA during development. Furthermore, we determined if these parameters were sensitive to imipramine and N-acetylcysteine/deferoxamine (NAC/DFX). Our results demonstrated that animals subjected to chronic administration of branched-chain amino acids showed a decrease in sucrose intake without significant changes in body weight. We also observed an increase in adrenal gland weight and immobility time during the forced swimming test. However, treatment with imipramine and NAC/DFX reversed these changes in the behavioral tasks. In conclusion, this study demonstrates a link between MSUD and depression in rats. Moreover, this investigation reveals that the antidepressant action of NAC/DFX and imipramine might be associated with their capability to maintain pro-/anti-oxidative homeostasis.

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Section: Discussionmentioning

confidence: 97%

Behavioral Responses in Rats Submitted to Chronic Administration of Branched-Chain Amino Acids

et al. 2013

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“…The cystine-glutamate exchanger is the primary source of accumbens extracellular glutamate in vivo (Baker et al, 2002) and cocaine-induced downregulation of cystineglutamate exchange underlies the alterations in extracellular levels of glutamate and glutamate releasability observed following withdrawal from either contingent or noncontingent cocaine administration (Baker et al, 2003). Although it still remains to be determined precisely how Homer proteins interact with the cystine-glutamate exchanger or how postsynaptic scaffolding proteins influence presynaptic glutamate release, our finding that preventing the cocaineinduced reduction in long Homer isoforms reversed the effects of cocaine withdrawal upon extracellular glutamate content and glutamate releasability, points to a potential interaction between Homer and the cystine/glutamate exchanger in the expression of cocaine-induced glutamate neural pathologies relevant to addiction.…”

Section: Homer Proteins and The Regulation Of Glutamate Transmissionmentioning

confidence: 99%

Homer Isoforms Differentially Regulate Cocaine-Induced Neuroplasticity

Szumlinski

Abernathy

Oleson

et al. 2005

Neuropsychopharmacol

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Homer proteins modulate neuroplasticity in excitatory synapses and are dynamically regulated by cocaine. Whereas acute cocaine elevates immediate-early gene (short) isoforms of Homer1 in the nucleus accumbens, withdrawal from repeated cocaine administration downregulates the expression of constitutive Homer1 isoforms. The present study determined whether or not this downregulation in constitutive Homer expression in the accumbens is necessary for enduring alterations in cocaine-induced changes in the brain and behavior. The long vs short Homer isoforms were overexpressed in the rat nucleus accumbens during drug abstinence, and the adaptations elicited by repeated cocaine on glutamate transmission and motor behavior were measured. It was found that both chronic and acute overexpression of constitutive, but not short, Homer isoforms abolished cocaine-induced sensitization of locomotor hyperactivity and prevented the development of glutamate abnormalities in the accumbens, including the reduction in basal extracellular glutamate content and the sensitized glutamate response to a subsequent cocaine challenge injection. Together, these data indicate that the enduring reduction of long Homer isoforms in the nucleus accumbens of cocaine-withdrawn rats is necessary for the expression of cocaine-induced neuroplasticity.

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“…Nonvesicular glutamate may be another potential source of glutamate that could contribute to potentiation. Psychostimulants promote glutamate efflux in the VTA (Kalivas and Duffy, 1995;Xue et al, 1996;Wolf and Xue, 1998), due to efflux from glutamate transporters and cystine-glutamate exchangers (Wolf and Xue 1999;Baker et al, 2002Baker et al, , 2003. In principle, this rise in extracellular glutamate could contribute to the development of LTP, but studies indicate that this rise does not begin until 2 h after psychostimulant exposure (Xue et al, 1996;Wolf and Xue, 1998).…”

Section: Changes In Ampar/nmdar Ratio Are Rapidmentioning

confidence: 99%

Rapid Synaptic Plasticity of Glutamatergic Synapses on Dopamine Neurons in the Ventral Tegmental Area in Response to Acute Amphetamine Injection

Faleiro

Jones

Kauer

2004

Neuropsychopharmacol

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Drugs of abuse activate the reward circuitry of the mesocorticolimbic system, and it has been hypothesized that drug exposure triggers synaptic plasticity of glutamatergic synapses onto dopamine (DA) neurons of the ventral tegmental area. Here, we show that just a 2 h in vivo exposure to amphetamine is sufficient to potentiate these synapses, measured as an increase in the synaptic AMPAR/NMDAR ratio. We tested the prediction that an increase in GluR1-containing AMPA receptors would result in an increase in GluR1 homomeric receptors at synapses, but were unable to observe any evidence of the predicted rectification in DA neurons from animals treated with amphetamine. We also examined the possibility of increased AMPA receptor insertion in the membrane, but did not detect a significant increase in biotinylated surface GluR1. We conclude that amphetamine induces rapid changes in synaptic AMPAR/NMDAR ratios, suggesting that potentiation of glutamatergic synapses is a relatively early event in the series of neuroadaptations in response to drugs of abuse.

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The Origin and Neuronal Function ofIn VivoNonsynaptic Glutamate

Cited by 532 publications

References 64 publications

Behavioral Responses in Rats Submitted to Chronic Administration of Branched-Chain Amino Acids

Behavioral Responses in Rats Submitted to Chronic Administration of Branched-Chain Amino Acids

Homer Isoforms Differentially Regulate Cocaine-Induced Neuroplasticity

Rapid Synaptic Plasticity of Glutamatergic Synapses on Dopamine Neurons in the Ventral Tegmental Area in Response to Acute Amphetamine Injection

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