Distribution of the messenger RNA for a metabotropic glutamate receptor, mGluR2, in the central nervous system of the rat

Ohishi, Hitoshi; Shigemoto, Ryuichi; Nakanishi, Shigetada; Mizuno, Noboru

doi:10.1016/0306-4522(93)90485-x

Cited by 514 publications

(257 citation statements)

References 30 publications

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“…The expression pattern of mGluR2 and mGluR3 was in agreement with previous findings (Ohishi et al, 1993;Tanabe et al, 1993), and showed the highest expression levels for both genes in the cortex and dentate gyrus of the hippocampus (Supplementary Figure S10). No significant differences in mGluR2 and mGluR3 expression were found between 0crit and 3crit rats in any investigated forebrain region.…”

Section: Resultssupporting

confidence: 90%

The mGluR2/3 Agonist LY379268 Induced Anti-Reinstatement Effects in Rats Exhibiting Addiction-like Behavior

Cannella

Halbout

Uhrig

et al. 2013

Neuropsychopharmacol

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Medication development for cocaine-addicted patients is difficult, and many promising preclinical candidates have failed in clinical trials. One reason for the difficulty in translating preclinical findings to the human condition is that drug testing is typically conducted in behavioral procedures in which animals do not show addiction-like traits. Recently, a DSM-IV-based animal model has been developed that allows studying the transition to an addiction-like behavior. Changes in synaptic plasticity are involved in the transition to cocaine addiction. In particular, it has been shown that metabotropic glutamate receptor 2/3 (mGluR2/3)-mediated long-term depression is suppressed in the prelimbic cortex in addict-like rats. We therefore hypothesized that cocaine-seeking in addict-like rats could be treated with an mGluR2/3 agonist. Indeed, addict-like rats that were treated systemically with the mGluR2/3 agonist LY379268 (0, 0.3, and 3 mg/kg) showed a pronounced reduction in cue-induced reinstatement of cocaine-seeking. In an attempt to dissect the role played by mGluR2 and mGluR3 in cue-induced reinstatement, we analyzed the mRNA expression patterns in several relevant brain areas but did not find any significant differences between cocaine addict-like and non-addict-like rats, suggesting that the behavioral differences observed are due to translational rather than transcriptional regulation. Another possibility to study the contributions of mGluR2 and mGluR3 in mediating addictive-like behavior is the use of knockout models. Because mGluR2 knockouts cannot be used in operant procedures due to motoric impairment, we only tested mGluR3 knockouts. These mice did not differ from controls in reinstatement, suggesting that mGluR2 receptors are critical in mediating addictive-like behavior.

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Section: Resultssupporting

confidence: 90%

The mGluR2/3 Agonist LY379268 Induced Anti-Reinstatement Effects in Rats Exhibiting Addiction-like Behavior

Cannella

Halbout

Uhrig

et al. 2013

Neuropsychopharmacol

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“…These may reflect differences in desensitization factors (3,66,136); regulation of intracellular calcium signaling (93); interactions with iGluRs and ion channels via homer; PSD-95 complexes and Shank (30,92,168,199,200); signaling through various heterotrimeric Gprotein subunits (45,67); regulation of mGluR mediated responses by regulators of G-protein signaling proteins (161); or expression pattern differences attributable to anatomical location (131,132,169,196), ontogeny (11,23,41,71,155,172,174), injury (64,76,88,117,119), or disease (4,12,27,43,132,156,175).…”

Section: Mglurs and Neuroprotectionmentioning

confidence: 99%

Metabotropic Glutamate Receptor Subtype 5 Antagonists MPEP and MTEP

2006

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Glutamate regulates the function of central nervous system (CNS), in part, through the cAMP and/or IP3/DAG second messenger-associated metabotropic glutamate receptors (mGluRs). The mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) has been extensively used to elucidate potential physiological and pathophysiological functions of mGluR5. Unfortunately, recent evidence indicates significant non-specific actions of MPEP, including inhibition of NMDA receptors. In contrast, in vivo and in vitro characterization of the newer mGluR5 antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) indicates that it is more highly selective for mGluR5 over mGluR1, has no effect on other mGluR subtypes, and has fewer off-target effects than MPEP. This article reviews literature on both of these mGluR5 antagonists, which suggests their possible utility in neurodegeneration, addiction, anxiety and pain management.

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“…In situ hybridization experiments were performed as described previously (Shigemoto et al, 1992;Ohishi et al, 1993). Briefly, adult male Sprague Dawley rats (n ϭ 2; 250 -300 g) were deeply anesthetized with ether and decapitated.…”

Section: Double-and Triple-immunofluorescent Experimentsmentioning

confidence: 99%

Metabotropic Glutamate Receptor 8-Expressing Nerve Terminals Target Subsets of GABAergic Neurons in the Hippocampus

Ferraguti¹,

Klausberger²,

Cobden³

et al. 2005

J. Neurosci.

121

138

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Presynaptic metabotropic glutamate receptors (mGluRs) show a highly selective expression and subcellular location in nerve terminals modulating neurotransmitter release. We have demonstrated that alternatively spliced variants of mGluR8, mGluR8a and mGluR8b, have an overlapping distribution in the hippocampus, and besides perforant path terminals, they are expressed in the presynaptic active zone of boutons making synapses selectively with several types of GABAergic interneurons, primarily in the stratum oriens. Boutons labeled for mGluR8 formed either type I or type II synapses, and the latter were GABAergic. Some mGluR8-positive boutons also expressed mGluR7 or vasoactive intestinal polypeptide. Interneurons strongly immunopositive for the muscarinic M2 or the mGlu1 receptors were the primary targets of mGluR8-containing terminals in the stratum oriens, but only neurochemically distinct subsets were innervated by mGluR8-enriched terminals. The majority of M2-positive neurons were mGluR8 innervated, but a minority, which expresses somatostatin, was not. Rare neurons coexpressing calretinin and M2 were consistently targeted by mGluR8-positive boutons. In vivo recording and labeling of an mGluR8-decorated and strongly M2-positive interneuron revealed a trilaminar cell with complex spike bursts during theta oscillations and strong discharge during sharp wave/ripple events. The trilaminar cell had a large projection from the CA1 area to the subiculum and a preferential innervation of interneurons in the CA1 area in addition to pyramidal cell somata and dendrites. The postsynaptic interneuron type-specific expression of the high-efficacy presynaptic mGluR8 in both putative glutamatergic and in identified GABAergic terminals predicts a role in adjusting the activity of interneurons depending on the level of network activity.

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Distribution of the messenger RNA for a metabotropic glutamate receptor, mGluR2, in the central nervous system of the rat

Cited by 514 publications

References 30 publications

The mGluR2/3 Agonist LY379268 Induced Anti-Reinstatement Effects in Rats Exhibiting Addiction-like Behavior

The mGluR2/3 Agonist LY379268 Induced Anti-Reinstatement Effects in Rats Exhibiting Addiction-like Behavior

Metabotropic Glutamate Receptor Subtype 5 Antagonists MPEP and MTEP

Metabotropic Glutamate Receptor 8-Expressing Nerve Terminals Target Subsets of GABAergic Neurons in the Hippocampus

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