Amphetamine Induces Differential Changes in the Gene Expression of Metabotropic Glutamate Receptor 5 in Cultured Cortical and Hippocampal Neurons

Yu, Meng-Fen; Lin, Tzu-Yuung; Ho, Wen-Hsin; Yin, Hsiang‐Shu

doi:10.1385/jmn:17:1:13

Cited by 11 publications

(7 citation statements)

References 27 publications

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“…Our earlier study recorded that the antagonist of mGluRs, MCPG, counteracted about 58% of the AMPH-elevated level (37%) of mGluR5 mRNA in cortical cultured neurons, supporting an association between AMPH and the receptor (Yu et al, 2001). Similarly, another study on cortical neuron culture suggests that an interacting relationship exists between AMPH and the NMDA receptor, because the radioligand binding capacity of the receptor was weakened when the binding assay was performed in the presence of AMPH (Yamamoto et al, 1996).…”

Section: Activity Of Mglur5 In Amph-treated Cultured Neuronsmentioning

confidence: 74%

“…Cytosine arabinoside (1 M) was used to prevent the proliferation of nonneuronal cells. In the culture, about 90% of cortical cells and 91% of hippocampal cells were neurons, which were verified by immunostaining with a specific anti-neurofilament 200 kDa antibody (Yu et al, 2001).…”

Section: Materials and Methods Neuron Culture And Drug Treatmentmentioning

confidence: 80%

“…Primary neuron cultures were prepared from the brains of 18-day-old rat embryos, as described previously (Brewer and Cotman, 1989;Yu et al, 2001). Briefly, pregnant female Wistar rats were anesthetized with diethyl ether and the embryos were removed.…”

Section: Materials and Methods Neuron Culture And Drug Treatmentmentioning

confidence: 99%

“…We have previously shown that through interacting with ␣-methyl-4-carboxyphenylglycine (MCPG)-sensitive receptors, short-term (1-3 h) AMPH treatment raised the gene expression of mGluR5 in cultured cortical and hippocampal neurons (Yu et al, 2001). In addition, it has been found that via group I mGluRs, acute AMPH could facilitate the phosphorylation of CREB, Elk-1, and ERK 1/2 signaling proteins and FOS gene expression, as shown by immunocytochemistry and immunoblotting (Choe et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Activation of metabotropic glutamate receptor 5 is associated with effect of amphetamine on brain neurons

Lin

et al. 2003

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The role of metabotropic glutamate receptor 5 (mGluR5) was explored in mechanisms underlying the action of amphetamine (AMPH). The activity of mGluR5 was monitored by measuring the level of [3H]inositol monophosphates in brain neurons, in response to stimulation of 2-choloro-5-hydroxyphenylglycine (CHPG), a selective agonist of mGluR5. Treatment with 1 microM of AMPH for 1 h or 7 days increased the CHPG (1 mM, 30 min)-evoked phosphoinositide turnover by 46% or 92% and 26% or 84% in cultured cortical and hippocampal neurons, respectively, from that of CHPG-only treated cells. When AMPH was present during CHPG application post-1 h or 7 day AMPH incubation, the rate of phosphoinositide hydrolysis in cortical neurons became 121% or 142% higher than that treated with CHPG only. The postnatal day (P) 21 (juvenile) and P60 (adult) rats received three intraperitoneal injections of 5 mg/kg of AMPH or saline daily for 6 days. They were challenged on the eighth day with one dosage and sacrificed 3 h later. Reversible 3H-glutamate binding detected increases of 22-89% in the binding levels of cortex and hippocampus of both ages following the AMPH injections. Increases of 13-18% in the levels of mGluR5 mRNA were seen in the juvenile pyramidal neurons of hippocampal CA1-4, granular cells of dentate gyrus, and ventral thalamic nuclei, as shown by in situ hybridization. The AMPH-induced altered activity of mGluR5 is probably associated with changes in the expression of the glutamate receptors, including mGluR5. AMPH may modify the sensitivity of mGluR5 or interact with the receptor itself.

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Section: Activity Of Mglur5 In Amph-treated Cultured Neuronsmentioning

confidence: 74%

Section: Materials and Methods Neuron Culture And Drug Treatmentmentioning

confidence: 80%

Section: Materials and Methods Neuron Culture And Drug Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Activation of metabotropic glutamate receptor 5 is associated with effect of amphetamine on brain neurons

Lin

et al. 2003

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“…Thus, the inability of MPEP to prevent amphetamineinduced behavioral sensitization is not likely due to an adaptive up-regulation of mGlu5 receptor expression in these forebrain regions. On the other hand, in vivo and in vitro studies have shown that cortical or hippocampal neurons increase expression of mGlu5 in response to amphetamine [139,140]. Thus, more research is needed to determine if altered mGlu5 expression induced by repeated amphetamine administration contributes to the inability of MPEP to inhibit the development of behavioral sensitization to this psychostimulant.…”

Section: Cocainementioning

confidence: 99%

mGlu5 Receptors: Neuroanatomy, Pharmacology, and Role in Drug Addiction

Olive

2005

CPSR

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Over the past half century, most studies investigating the neural substrates of drug addiction have focused on the mesolimbic dopamine reward circuitry. Yet recent evidence suggests a critical role for glutamate neurotransmission in addiction-related behaviors. Glutamate receptors, both ionotropic and metabotropic, are widely expressed throughout the central nervous system. Dissection of the role of individual glutamate receptor subtypes in addictive processes has been aided by the development of pharmacological ligands selective for glutamate receptor subtypes, and by the generation of genetically altered rodents in which the gene encoding an individual glutamate receptor protein or receptor subunit has been deleted or altered. A pivotal study identifying a specific role for the type 5 metabotropic glutamate receptor (mGlu5) in drug addiction was published in 2001 by Chiamulera and colleagues. These investigators demonstrated that mice lacking functional mGlu5 receptors failed to self-administer cocaine and did not exhibit cocaine-induced hyperlocomotion, while food seeking behavior remained unaltered. These findings, and a subsequent flurry of other animal studies utilizing selective mGlu5 antagonists, have confirmed that inhibition of mGlu5 receptor function reduces drug self-administration and/or other behaviors induced by abused drugs including cocaine, amphetamine, nicotine, and alcohol. In this paper these preclinical studies demonstrating a clear role for mGlu5 receptors in drug addiction are reviewed. Summaries of the neuroanatomical distribution, pharmacology and neurotransmitter release-altering properties of mGlu5 receptors are also given. From this review, it is clear that additional studies are needed to determine (1) the efficacy of mGlu5 antagonists in reducing selfadministration of all drugs of abuse, (2) neuroanatomical loci and neurochemical mechanisms by which mGlu5 regulate addictive behaviors, (3) the efficacy of mGlu5 antagonists in various models of craving and relapse, and (4) the ability of mGlu5 antagonists to alter various forms of neuronal plasticity associated with acute or chronic drug exposure. Such studies will hopefully prove a basis for developing novel mGlu5-based pharmacotherapies to aid in the treatment of drug addiction in humans.

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Glutamatergic substrates of drug addiction and alcoholism

Gass

Olive

2008

Biochemical Pharmacology

433

367

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The past two decades have witnessed a dramatic accumulation of evidence indicating that the excitatory amino acid glutamate plays an important role in drug addiction and alcoholism. The purpose of this review is to summarize findings on glutamatergic substrates of addiction, surveying data from both human and animal studies. The effects of various drugs of abuse on glutamatergic neurotransmission are discussed, as are the effects of pharmacological or genetic manipulation of various components of glutamate transmission on drug reinforcement, conditioned reward, extinction, and relapse-like behavior. In addition, glutamatergic agents that are currently in use or are undergoing testing in clinical trials for the treatment of addiction are discussed, including acamprosate, N-acetylcysteine, modafinil, topiramate, lamotrigine, gabapentin and memantine. All drugs of abuse appear to modulate glutamatergic transmission, albeit by different mechanisms, and this modulation of glutamate transmission is believed to result in long-lasting neuroplastic changes in the brain that may contribute to the perseveration of drug-seeking behavior and drug-associated memories. In general, attenuation of glutamatergic transmission reduces drug reward, reinforcement, and relapse-like behavior. On the other hand, potentiation of glutamatergic transmission appears to facilitate the extinction of drug-seeking behavior. However, attempts at identifying genetic polymorphisms in components of glutamate transmission in humans have yielded only a limited number of candidate genes that may serve as risk factors for the development of addiction. Nonetheless, manipulation of glutamatergic neurotransmission appears to be a promising avenue of research in developing improved therapeutic agents for the treatment of drug addiction and alcoholism.

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Amphetamine Induces Differential Changes in the Gene Expression of Metabotropic Glutamate Receptor 5 in Cultured Cortical and Hippocampal Neurons

Cited by 11 publications

References 27 publications

Activation of metabotropic glutamate receptor 5 is associated with effect of amphetamine on brain neurons

Activation of metabotropic glutamate receptor 5 is associated with effect of amphetamine on brain neurons

mGlu5 Receptors: Neuroanatomy, Pharmacology, and Role in Drug Addiction

Glutamatergic substrates of drug addiction and alcoholism

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