Metabotropic Glutamate Receptors and Dopamine Receptors Cooperate to Enhance Extracellular Signal-Regulated Kinase Phosphorylation in Striatal Neurons

Voulalas, Pamela J.; Holtzclaw, Lynne A.; Wolstenholme, Jennifer T.; Russell, James T.; Hyman, Steven E.

doi:10.1523/jneurosci.4574-04.2005

Cited by 68 publications

(49 citation statements)

References 67 publications

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“…Moreover, both D1R and NMDA receptors in the accumbens appear critical for the early consolidation of appetitive Pavlovian memories (Dalley et al, 2005). These reports are particularly relevant in the context of our current findings, given the close interactions between mGluR5 and D1R (Paolillo et al, 1998;Voulalas et al, 2005;Schotanus and Chergui, 2008) and NMDA receptors (Pisani et al, 2001;Mao and Wang, 2002;Choe et al, 2006) in the striatum. Thus, it is possible that impaired incentive learning and relapse-like behaviors in mGluR5 KD-D1 mice were due, in part, to changes in striatal D1R and NMDA receptor function as a consequence of mGluR5 loss.…”

Section: Discussionsupporting

confidence: 58%

“…Although mGluR5 is densely expressed on both D1-and D2-MSN populations (Tallaksen-Greene et al, 1998), converging lines of research would suggest that mGluR5 located specifically on D1-MSNs is ideally positioned to influence associative reward-learning processes that may underpin relapse triggered by drug-paired stimuli. First, there is evidence that striatal dopamine D1 receptors (D1R) play a critical role in both the consolidation of associative reward-learning memories (Dalley et al, 2005) and many of the long-term effects of addictive drugs (Anderson and Pierce, 2005) and second, mGluR5 appears to interact closely with D1Rs to regulate striatal neurotransmission (Paolillo et al, 1998;Voulalas et al, 2005;Schotanus and Chergui, 2008).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Incentive Learning Underlying Cocaine-Seeking Requires mGluR5 Receptors Located on Dopamine D1 Receptor-Expressing Neurons

Novák¹,

Halbout²,

O’Connor³

et al. 2010

J. Neurosci.

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Understanding the psychobiological basis of relapse remains a challenge in developing therapies for drug addiction. Relapse in cocaine addiction often occurs following exposure to environmental stimuli previously associated with drug taking. The metabotropic glutamate receptor, mGluR5, is potentially important in this respect; it plays a central role in several forms of striatal synaptic plasticity proposed to underpin associative learning and memory processes that enable drug-paired stimuli to acquire incentive motivational properties and trigger relapse. Using cell type-specific RNA interference, we have generated a novel mouse line with a selective knock-down of mGluR5 in dopamine D1 receptor-expressing neurons. Although mutant mice self-administer cocaine, we show that reinstatement of cocaineseeking induced by a cocaine-paired stimulus is impaired. By examining different aspects of associative learning in the mutant mice, we identify deficits in specific incentive learning processes that enable a reward-paired stimulus to directly reinforce behavior and to become attractive, thus eliciting approach toward it. Our findings show that glutamate signaling through mGluR5 located on dopamine D1 receptor-expressing neurons is necessary for incentive learning processes that contribute to cue-induced reinstatement of cocaineseeking and which may underpin relapse in drug addiction.

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Section: Discussionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Incentive Learning Underlying Cocaine-Seeking Requires mGluR5 Receptors Located on Dopamine D1 Receptor-Expressing Neurons

Novák¹,

Halbout²,

O’Connor³

et al. 2010

J. Neurosci.

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“…These discrepancies can both be explained if these MSNs express higher levels of mGluR5 than mGluR1 such that a fraction of mGluR5 signaling is coordinated with mGluR1 signaling, as in SCG neurons, but another subset acts independently. Indeed, despite the evidence that MSNs express both mGluR1 and mGluR5 (Shigemoto et al, 1992(Shigemoto et al, , 1993Pisani et al, 2001;Gubellini et al, 2004), some data indicate that the group I mGluR-mediated calcium responses in these cells are primarily mediated via mGluR5 (Voulalas et al, 2005). Note that if mGluR1 and mGluR5 signal entirely independently, no additional reduction in the DHPG response would be expected with these inhibitors applied together versus each applied alone, since both target mGluR1.…”

Section: Functional Interaction Of Mglur1 and Mglur5mentioning

confidence: 99%

Cooperative Signaling between Homodimers of Metabotropic Glutamate Receptors 1 and 5

Sevastyanova

Kammermeier

2014

Mol Pharmacol

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Metabotropic glutamate receptors (mGluRs) function as dimers. Recent work suggests that mGluR1 and mGluR5 may physically interact, but the nature and functional consequences of this relationship have not been addressed. In this study, the functional and pharmacological consequences of this interaction were investigated. Using heterologous expression of mGluR cDNA in rat sympathetic neurons from the superior cervical ganglion and inhibition of the native calcium currents as an assay for receptor activation, a functional interdependence between mGluR1 and mGluR5 was demonstrated. In neurons coexpressing these receptors, combining a selective mGluR1 competitive antagonist with either an mGluR1-or mGluR5-selective negative allosteric modulator[2-methyl-6-(phenylethynyl)pyridine hydrochloride], respectively, strongly occluded signaling by both receptors to an approximately equal degree. By contrast, in cells coexpressing mGluR1 and mGluR2, combining the same mGluR1 competitive inhibitor with an mGluR1 or mGluR2 NAM yielded partial and full inhibition of the response, respectively, as expected for independently acting receptors. In neurons expressing mGluR1 and mGluR5, the selective NAMs each strongly inhibited the response to glutamate, suggesting that these receptors do not interact as heterodimers, which would not be inhibited by selective NAMs. Finally, evidence for a similar mGluR1/mGluR5 functional dependence is shown in medium spiny striatal neurons.Together, these data demonstrate cooperative signaling between mGluR1 and mGluR5 in a manner inconsistent with heterodimerization, and thus suggest an interaction between homodimers.

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“…In addition to being a downstream effector of MAPK/ERK signaling (Bonni et al, 1999;Dolmetsch et al, 2001;Frodin and Gammeltoft, 1999;Morikawa et al, 2004;Vanhoutte et al, 1999;Voulalas et al, 2005), CREB activity is regulated by several other signaling pathways including PI3K/ Akt (Perkinton et al, 1999), protein kinase A (Impey et al, 1998;Vitolo et al, 2002), Ca 2+ / calmodulin-dependent protein kinase IV (Deisseroth et al, 1998;Redmond et al, 2002), and protein kinase C (PKC) (Roberson et al, 1999;Zhao and Brinton, 2003). In neurons, CREB activation is known to regulate a variety of neurotrophic and neuroprotective effects (Crino et al, 1998;Finkbeiner, 2000;Kelly et al, 2000).…”

Section: Androgen Activation Of Creb Signalingmentioning

confidence: 99%

Androgen cell signaling pathways involved in neuroprotective actions

Pike

Nguyen

Ramsden

et al. 2008

Hormones and Behavior

114

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As a normal consequence of aging in men, testosterone levels significantly decline in both serum and brain. Age-related testosterone depletion results in increased risk of dysfunction and disease in androgen-responsive tissues, including brain. Recent evidence indicates that one deleterious effect of age-related testosterone loss in men is increased risk for Alzheimer's disease (AD). We discuss recent findings from our laboratory and others that identify androgen actions implicated in protecting the brain against neurodegenerative diseases and begin to define androgen cell signaling pathways that underlie these protective effects. Specifically, we focus on the roles of androgens as (1) endogenous negative regulators of β-amyloid accumulation, a key event in AD pathogenesis, and (2) neuroprotective factors that utilize rapid non-genomic signaling to inhibit neuronal apoptosis. Continued elucidation of cell signaling pathways that contribute to protective actions of androgens should facilitate the development of targeted therapeutic strategies to combat AD and other agerelated neurodegenerative diseases.

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Metabotropic Glutamate Receptors and Dopamine Receptors Cooperate to Enhance Extracellular Signal-Regulated Kinase Phosphorylation in Striatal Neurons

Cited by 68 publications

References 67 publications

Incentive Learning Underlying Cocaine-Seeking Requires mGluR5 Receptors Located on Dopamine D1 Receptor-Expressing Neurons

Incentive Learning Underlying Cocaine-Seeking Requires mGluR5 Receptors Located on Dopamine D1 Receptor-Expressing Neurons

Cooperative Signaling between Homodimers of Metabotropic Glutamate Receptors 1 and 5

Androgen cell signaling pathways involved in neuroprotective actions

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