Localization of mGluR1a-like immunoreactivity and mGluR5-like immunoreactivity in identified populations of striatal neurons

Tallaksen-Greene, Sara J.; Kaatz, Kevin W.; Romano, Carmelo; Albin, Roger L.

doi:10.1016/s0006-8993(97)01141-4

Cited by 201 publications

(132 citation statements)

References 47 publications

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“…Coexpression of both mGluR1a and mGluR5 has been reported in the STN, the SNr, and the striatum, three nuclei of the BG circuitry (Tallaksen-Greene et al, 1998;Awad et al, 2000;Marino et al, 2001). However, the DHPG-induced depolarization and the potentiation of NMDA receptor currents in the STN is mediated solely by mGluR5, whereas activation of mGluR1 only is responsible for depolarization and induction of a slow EPSP in SNr neurons Marino et al, 2001).…”

Section: Pharmacology Of the Dhpg-induced Depolarization In The Gpmentioning

confidence: 97%

“…Group I mGluRs are both present in the globus pallidus (GP), the subthalamic nucleus (STN), the substantia nigra pars reticulata (SNr), and the striatum (Tallaksen-Greene et al, 1998;Hanson and Smith, 1999;Awad et al, 2000;Marino et al, 2001) (for review, see Rouse et al, 2000). Metabotropic GluR1 and mGluR5 carry distinct functions in the STN, SNr, and the striatum in which they colocalize to the same neurons (Pisani et al, 2001a;Marino et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Distinct Functional Roles of the Metabotropic Glutamate Receptors 1 and 5 in the Rat Globus Pallidus

Poisik¹,

Mannaioni²,

Traynelis³

et al. 2003

J. Neurosci.

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Group I metabotropic glutamate receptors (mGluRs) 1 and 5 frequently colocalize in the same neurons throughout the CNS. Because both receptors can couple to the same effector systems, the purpose of their cellular coexpression remains unclear. Here, we report that group I mGluR1 and mGluR5 have distinct functional roles in type II neurons of the rat globus pallidus (GP). Type II GP neurons form a large population of GABAergic projection neurons that are characterized by the presence of inwardly rectifying current I h , low-threshold voltage-activated calcium current I t , and activity at rest. Although immunocytochemical analysis reveals a high degree of neuronal colocalization of the two group I mGluRs in the GP, activation of mGluR1 only directly depolarizes type II GP neurons. Interestingly, blockade of mGluR5 by a highly selective antagonist, methylphenylethynylpyridine, leads to the potentiation of the mGluR1-mediated depolarization in this neuronal subpopulation. Metabotropic GluR1 desensitizes during repeated activation with the agonist in type II GP neurons, and blocking mGluR5 prevents the desensitization of the mGluR1-mediated depolarization. Elimination of the activity of protein kinase C (PKC) by an application of 1 M bisendolylmaleimide or 1 M chelerythrine, both protein kinase C inhibitors, potentiates the mGluR1-mediated response and prevents the desensitization of mGluR1 in type II GP neurons, suggesting that the effect of mGluR5 on mGluR1 signaling may involve PKC. Together, these data illustrate a novel mechanism by which mGluR1 and mGluR5, members of the same family of G-protein-coupled receptors, can interact to modulate neuronal activity in the rat GP.

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Section: Pharmacology Of the Dhpg-induced Depolarization In The Gpmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Distinct Functional Roles of the Metabotropic Glutamate Receptors 1 and 5 in the Rat Globus Pallidus

Poisik¹,

Mannaioni²,

Traynelis³

et al. 2003

J. Neurosci.

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“…In addition, group I mGlu receptors are present in the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr) (Tallaksen-Greene et al, 1998;Testa et al, 1994). In the striatum, adenosine A 2A receptors are predominantly expressed by g-amino butyric acid (GABA)-enkephalin striatopallidal neurons, where they colocalize with DA D 2 receptors (Fink et al, 1992;MartinezMir et al, 1991) and are also present in 25% of cholinergic interneurons (Schiffmann et al, 1991;Fredholm et al, 2001).…”

Section: Functional Interaction Between a 2a And Mglu 5 Receptorsmentioning

confidence: 99%

“…A growing number of studies in animal models of PD suggest that counteracting glutamatergic hyperactivity by pharmacological blockade of glutamate transmission in the basal ganglia represents the most recent challenge in the treatment of Parkinsonian patients (Rouse et al, 2000). Owing to their high level of expression in the basal ganglia structures: striatum, the internal pallidum and substantia nigra pars reticulata (Testa et al, 1994;Tallaksen-Greene et al, 1998), the group I metabotropic glutamate receptors play a major role in the regulation of these nuclei (Rouse et al, 2000). Indeed, recent studies in rats have emphasized the anti-Parkinsonian action of the selective mGluR antagonist of subtype 5 (mGlu 5 receptor) 2-methyl-6-(phenylethylnyl)-pyridine (MPEP) in 6-OHDA-lesioned rats (Spooren et al, 2000;Breysse et al, 2002Breysse et al, , 2003.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Blockade of Adenosine A2A and Metabotropic Glutamate mGlu5 Receptors Increase their Efficacy in Reversing Parkinsonian Deficits in Rats

Coccurello

Breysse

Amalric

2004

Neuropsychopharmacol

117

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Recent evidence suggest that antagonism of adenosine A 2A receptors represent an alternative therapeutic approach to Parkinson's disease (PD). Coactivation of A 2A and the glutamate subtype 5 metabotropic receptors (mGlu 5 ) synergistically stimulates DARPP-32 phosphorylation and c-fos expression in the striatum. This study therefore tested the effects of a joint blockade of these receptors to alleviate the motor dysfunction in a rat model of PD. 6-Hydroxydopamine infusions in the striatum produced akinetic deficits in rats trained to release a lever after a stimulus in a reaction time (RT) task. At 2 weeks after the lesion, A 2A and mGlu 5 receptors selective antagonists 8-(3-chlorostyryl)caffeine (CSC) and 2-methyl-6-(phenylethynyl)-pyridine (MPEP) were administered daily for 3 weeks either as a single or joint treatment. Injections of CSC (1.25 mg/kg) and MPEP (1.5 mg/kg) separately or in combination reduced the increase of delayed responses and RTs induced by 6-OHDA lesions, while the same treatment had no effect in controls. Furthermore, coadministration of lower doses of 0.625 mg/kg CSC and 0.375 mg/kg MPEP noneffective as a single treatment promoted a full and immediate recovery of akinesia, which was found to be more efficient than the separate blockade of these receptors. These results demonstrate that the combined inactivation of A 2A and mGlu 5 receptor potentiate their beneficial effects supporting this pharmacological strategy as a promising anti-Parkinsonian therapy.

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“…The highest density is, therefore, in areas related to processing of motivated behaviours and emotions such as the limbic system and the extended amygdala (Swanson et al 2005). At the striatal level, Group I mGluRs co-localize with dopamine (DA) receptors (Tallaksen-Greene et al 1998) and are involved in the regulation of DA release in nucleus accumbens (Taber and Fibiger 1995). Moreover, agonists of Group I mGluRs increase locomotor activity in a DA-dependent manner (Kim and Vezina 1998).…”

mentioning

confidence: 99%

Metabotropic glutamate receptor 5 as a potential target for smoking cessation

2016

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RationaleMost habitual smokers find it difficult to quit smoking because they are dependent upon the nicotine present in tobacco smoke. Tobacco dependence is commonly treated pharmacologically using nicotine replacement therapy or drugs, such as varenicline, that target the nicotinic receptor.Relapse rates, however, remain high and there remains a need to develop novel non-nicotinic pharmacotherapies for the dependence that are more effective than existing treatments. ObjectiveThe purpose of this paper is to review the evidence from preclinical and clinical studies that drugs that antagonise the metabotropic glutamate receptor 5 (mGluR5) in the brain are likely to be efficacious as treatments for tobacco dependence. ResultsImaging studies reveal that chronic exposure to tobacco smoke reduces the density of mGluR5s in human brain. Preclinical results demonstrate that negative allosteric modulators (NAMs) at mGluR5 attenuate both nicotine self-administration and the reinstatement of responding evoked by exposure to conditioned cues paired with nicotine delivery. They also attenuate the effects of nicotine on brain dopamine pathways implicated in addiction. ConclusionsAlthough mGluR5 NAMs attenuate most of the key facets of nicotine dependence they potentiate the symptoms of nicotine withdrawal. This may limit their value as smoking cessation aids. The NAMs that have been employed most widely in preclinical studies of nicotine dependence have too many "off target" effects to be used clinically. However newer mGluR5 NAMs have been developed for clinical use in other indications. Future studies will determine if these agents can also be used effectively and safely to treat tobacco dependence.

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Localization of mGluR1a-like immunoreactivity and mGluR5-like immunoreactivity in identified populations of striatal neurons

Cited by 201 publications

References 47 publications

Distinct Functional Roles of the Metabotropic Glutamate Receptors 1 and 5 in the Rat Globus Pallidus

Distinct Functional Roles of the Metabotropic Glutamate Receptors 1 and 5 in the Rat Globus Pallidus

Simultaneous Blockade of Adenosine A2A and Metabotropic Glutamate mGlu5 Receptors Increase their Efficacy in Reversing Parkinsonian Deficits in Rats

Metabotropic glutamate receptor 5 as a potential target for smoking cessation

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