Group I mGluRs and Long-Term Depression: Potential Roles in Addiction?

Grueter, Brad A.; McElligott, Zoé A.; Winder, Danny G.

doi:10.1007/s12035-007-0037-7

Cited by 28 publications

(28 citation statements)

References 132 publications

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“…Investigating the molecular mechanisms underlying hippocampal mGluR-LTD is essential for understanding and treating diseases such as FXS and addiction (Grueter et al, 2007) in which synaptic plasticity abnormalities are displayed. Patients with FXS have cognitive deficits Koukoui and Chandhuri, 2007) and also anxiety and epilepsy symptoms, which could be due to impaired synaptic glutamate signaling or to disrupted interactions between mGluRs and interacting proteins such as Homer 1a (Penagarikano et al, 2007).…”

Section: The Pathological Significance Of Metabotropic Glutamate mentioning

confidence: 99%

Metabotropic Glutamate Receptor-Mediated Long-Term Depression: Molecular Mechanisms

2009

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Section: The Pathological Significance Of Metabotropic Glutamate mentioning

confidence: 99%

Metabotropic Glutamate Receptor-Mediated Long-Term Depression: Molecular Mechanisms

2009

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“…Again under these conditions, a 15 min application of methoxamine still produced robust LTD (66.7 ± 13.3%, N ¼ 5, po0.05, not significantly different from single methoxamine application p40.05; Figure 4b). LTD induced by group 1 mGluR receptors (that are coupled to Gq) in other brain regions has been shown to involve L-type voltage gated calcium channels (VGCCs; for review see Grueter et al, 2007). Thus, we hypothesized that a 1 -AR LTD might also require L-type calcium signals.…”

Section: Statisticsmentioning

confidence: 99%

“…a 1 -AR LTD in the BNST Is a Heterosynaptic Form of Plasticity LTD mediated via group I mGluRs remains the best characterized G aq -coupled receptor LTD and has been described in the cerebellum, hippocampus, cortex, dorsal and ventral striatum, ventral tegmental area, and BNST (Ito, 2001;Robbe et al, 2002;Malenka and Bear, 2004;Bellone and Luscher, 2005;Grueter et al, 2006, for review see Grueter et al, 2007). An interesting aspect exhibited by group I mGluR-LTD is a degree of promiscuity of mechanism depending on the synapse where the LTD is expressed.…”

Section: Ne Induces Ltd In a Time-dependent Mannermentioning

confidence: 99%

α1-Adrenergic Receptor-Induced Heterosynaptic Long-Term Depression in the Bed Nucleus of the Stria Terminalis Is Disrupted in Mouse Models of Affective Disorders

McElligott

Winder

2007

Neuropsychopharmacol

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The glutamatergic synapse in specific brain regions has been shown to be a site for convergence of stress and addictive substances. The bed nucleus of the stria terminalis (BNST), a nucleus that relays between higher order processing centers and classical reward and stress pathways, receives dense noradrenergic inputs that are known to influence behavioral paradigms of both anxiety and stress-induced relapse to drug seeking. a 1 -Adrenergic receptors (a 1 -ARs) within this region have been implicated in modulation of the HPA axis and anxiety responses. We found that application of an a 1 -AR agonist produced a long-term depression (LTD) of excitatory transmission in an acute mouse BNST slice preparation. This effect was mimicked by a 20 min, but not a 10 min, application of 100 mM norepinephrine (NE) in a prazosin-sensitive manner. This a 1 -AR LTD was independent of N-methyl-D-aspartate receptor (NMDAR) function unlike previously described a 1 -AR LTD in the hippocampus and visual cortex; however, it was dependent on the activation of L-type voltage gated calcium channels (VGCCs). In addition, a 1 -AR LTD was induced independently of the activation of mGluR5 which can also induce LTD in this region. Furthermore, a 1 -AR LTD was intact in mice receiving an intraperitoneal injection of cocaine but was disrupted in a 2a -AR and NE transporter (NET) knockout (KO) mice. Thus a loss of this plasticity at glutamatergic synapses in BNST could contribute to affective behavioral phenotypes of these mice.

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“…Metabotropic glutamate receptors (mGluRs) are class C G protein-coupled receptors with widespread nervous system expression that are involved in an array of important physiological and pathological processes (Schoepp 2001;Grueter et al, 2007;Moussawi and Kalivas 2010;Vinson and Conn, 2012). There are eight mammalian mGluR genes (GRM1-8), subdivided into three groups, I through III.…”

Section: Introductionmentioning

confidence: 99%

Functional and Pharmacological Characteristics of Metabotropic Glutamate Receptors 2/4 Heterodimers

Kammermeier

2012

Mol Pharmacol

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Metabotropic glutamate receptors (mGluRs) were thought until recently to function mainly as stable homodimers, but recent work suggests that heteromerization is possible. Despite the growth in available compounds targeting mGluRs, little is known about the pharmacological profile of mGluR heterodimers. Here, this question was addressed for the mGluR2/4 heterodimer, examined by coexpressing both receptors in isolated sympathetic neurons from the rat superior cervical ganglion (SCG), a native neuronal system with a null mGluR background. Under conditions that favor mGluR2/4 heterodimer formation, activation of the receptor was not evident with the mGluR2-selective agonist (2S,2ЈR,3ЈR)-2-(2Ј,3Ј-dicarboxycyclopropyl)glycine (DCG-IV) or with the mGluR4 selective agonist L-(ϩ)-2-amino-4-phosphonobutyric acid (L-AP4); however, full activation was apparent when both ligands were applied together, confirming that mGluR dimers require ligand binding in both subunits for full activation. Properties of allosteric modulators were also examined, including the findings that negative allosteric modulators (NAMs) have two binding sites per dimer and that positive allosteric modulators (PAMs) have only a single site per dimer. In SCG neurons, mGluR2/4 dimers were not inhibited by the mGluR2-selective NAM (Z)-1-[2-cycloheptyloxy-2-(2,6-dichlorophenyl)ethenyl]-1H-1,2,4-triazole (Ro 64-5229), supporting the two-site model. Furthermore, application of the mGluR4 selective PAMs N-(4-chloro-3-methoxyphenyl)-2-pyridinecarboxamide (VU0361737) or N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC) and combined application of mGluR4 PAMs with the mGluR2 selective PAM biphenyl indanone-A failed to potentiate glutamate responses through mGluR2/4, suggesting that mGluR2/4 heterodimers are not modulatable by PAMs that are currently available.

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Group I mGluRs and Long-Term Depression: Potential Roles in Addiction?

Cited by 28 publications

References 132 publications

Metabotropic Glutamate Receptor-Mediated Long-Term Depression: Molecular Mechanisms

Metabotropic Glutamate Receptor-Mediated Long-Term Depression: Molecular Mechanisms

α1-Adrenergic Receptor-Induced Heterosynaptic Long-Term Depression in the Bed Nucleus of the Stria Terminalis Is Disrupted in Mouse Models of Affective Disorders

Functional and Pharmacological Characteristics of Metabotropic Glutamate Receptors 2/4 Heterodimers

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