Selective involvement of mGlu1 receptors in corticostriatal LTD

Gubellini, Paolo; Saulle, Emilia; Centonze, Diego; Bonsi, Paola; Pisani, Antonio; Bernardi, Giorgio; Conquet, François; Calabresi, Paolo

doi:10.1016/s0028-3908(01)00021-1

Cited by 103 publications

(58 citation statements)

References 48 publications

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“…This functional coupling could result from the postsynaptic association of NMDA receptors with a complex of proteins, which includes different scaffolding proteins (eg PSD-95, Homer, Shank), but other receptors including mGluR5 are also linked to this complex (Kotecha et al, 2003), and activation of mGluR5 can lead to an enhancement of NMDA receptor function through phosphorylation by protein kinase C (Hermans and Challiss, 2001;Schoepp and Conn, 1993). The high affinity of MPEP for mGluR5 receptors, which is more than 1000-fold higher compared to NMDARs, makes it very unlikely that under the used conditions MPEP affects NMDARs directly (Oleary et al, 2000;Gubellini et al, 2001;Spooren et al, 2001;Kozela et al, 2003). In summary, the functional coupling of mGluR5 and NMDA receptor suggests that the blockade of mGluR5 by MPEP reduces glutamatergic signaling through NMDA receptors and thereby interacts with ethanol-seeking and relapse behavior.…”

Section: Discussionmentioning

confidence: 99%

mGluR5 Antagonist MPEP Reduces Ethanol-Seeking and Relapse Behavior

Bäckström

Bachteler

Koch

et al. 2003

Neuropsychopharmacol

235

178

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The glutamatergic system plays an important role in mediating neurobehavioral effects of ethanol. Metabotropic glutamate receptors subtype 5 (mGluR5) are modulators of glutamatergic neurotransmission and are abundant in brain regions known to be involved in ethanol self-administration. Here, we studied the effects of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a highly potent, noncompetitive mGlu5 receptor antagonist, on voluntary ethanol consumption and relapse behavior. For this purpose, we used two models for the measurement of relapse behavior: (i) reinstatement of ethanol-seeking behavior by drug-associated cues and (ii) the alcohol deprivation effect in long-term ethanol-consuming rats. In the first set of experiments, rats were trained to lever press for ethanol in the presence of a distinct set of cues. After extinction, the animals were exposed to the respective cues that initiated reinstatement of responding. A response-contingent ethanol prime further enhanced responding compared to the conditioned cues alone. Under these conditions, MPEP (0, 1, 3, and 10 mg/kg) attenuated ethanol seeking significantly and in a dose-related manner. However, at the highest dose, MPEP also decreased the number of inactive lever responses. In the second set of experiments, rats with 1 year of ethanol experience and repeated deprivation phases were used. A subchronic treatment with MPEP (twice daily; 0, 3, and 10 mg/kg) resulted in a significant and dose-dependent reduction of the alcohol deprivation effect (ADE). Although the same MPEP treatment regimen decreased baseline drinking, this effect was not as pronounced as on the ADE. These results show in two commonly used models of relapse to ethanol that pharmacological targeting of mGlu5 receptors may be a promising approach for the treatment of alcoholism.

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Section: Discussionmentioning

confidence: 99%

mGluR5 Antagonist MPEP Reduces Ethanol-Seeking and Relapse Behavior

Bäckström

Bachteler

Koch

et al. 2003

Neuropsychopharmacol

235

178

View full text Add to dashboard Cite

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“…Postsynaptic G-protein-coupled receptors implicated in the induction of HFS-LTD do not play a role in FPL-LTD. Activation of mGluRs has been shown to be involved in the induction of LTD at the corticostriatal synapse (Gubellini et al, 2001;Sung et al, 2001), which might be connected to dependence on phospholipase C (PLC) activation and/or IP 3 release (Sugiura et al, 2006). Blockade of mGluR group I receptors by MPEP (40 M) plus CPCCOEt (80 M) did not inhibit LTD induced by FPL (EPSC amplitude, 55 Ϯ 1.9%; n ϭ 6; p Ͻ 0.001) (Fig.…”

Section: Activation Of Mglurs D 2 Rs or Phospholipase C Is Not Needmentioning

confidence: 94%

“…More recently, it has been demonstrated that the activation of D 2 receptors facilitates LTD by reducing muscarinic (M 1 ) receptor tone at corticostriatal synapses, thereby facilitating the activation of L-type calcium channels . mGluRs also participate in LTD induction by stimulating increases in intracellular calcium or enhancing inositol phospholipid turnover in the MSNs themselves (Gubellini et al, 2001;Sung et al, 2001;Ronesi et al, 2004;Sugiura et al, 2006). At present it is not clear whether mGluR activation is necessary for LTD induction or has a modulatory role similar to that of the D 2 receptor.…”

Section: Introductionmentioning

confidence: 99%

Combined Activation of L-Type Ca2+ Channels and Synaptic Transmission Is Sufficient to Induce Striatal Long-Term Depression

Adermark

Lovinger²

2007

Journal of Neuroscience

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“…Striatal long-term potentiation (LTP) is a long-lasting increase in synaptic efficacy that requires activation of NMDA-type glutamate receptors (Calabresi et al, 1992b;Partridge et al, 2000;Spencer and Murphy, 2000) and D1 dopamine receptors (Kerr and Wickens, 2001;Reynolds et al, 2001). Striatal long-term depression (LTD), however, is a long-lasting decrease in synaptic strength and depends on a number of converging factors including activation of D2 dopamine receptors (Calabresi et al, 1992a(Calabresi et al, , 1997Choi and Lovinger, 1997) and type I metabotropic glutamate receptors (Gubellini et al, 2001;Sung et al, 2001), increases in postsynaptic intracellular calcium involving activation of L-type calcium channels (Calabresi et al, 1992a(Calabresi et al, , 1994Choi and Lovinger, 1997), and postsynaptic endocannabinoid release leading to activation of CB1 cannabinoid receptors (Gerdeman et al, 2002), but not NMDA receptors (Lovinger et al, 1993). Both forms of plasticity are induced by high-frequency stimulation (HFS) of striatal afferents, but expression of LTP versus LTD varies as a function of postnatal age of the animals.…”

Section: Introductionmentioning

confidence: 99%

Anandamide Regulates Postnatal Development of Long-Term Synaptic Plasticity in the Rat Dorsolateral Striatum

Ade¹,

Lovinger²

2007

J. Neurosci.

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Long-term changes in synaptic efficacy produced by high-frequency stimulation (HFS) of glutamatergic afferents to the rat dorsolateral striatum exhibit heterogeneity during early stages of postnatal development. Whereas HFS most often induces striatal long-term potentiation (LTP) in rats postnatal day 12 (P12)-P14, the same stimulation tends to induce long-term depression (LTD) at ages P16 -P34. Previous studies have shown that striatal LTD induction depends on retrograde endocannabinoid signaling and activation of the CB1 cannabinoid receptor. It is also known that levels of one of the primary endogenous CB1 receptor agonists, anandamide (AEA), increases during development in whole-brain samples. In the present study, we sought to determine whether this developmental increase in AEA also takes place in striatal tissue and whether increased AEA levels contribute to the postnatal switch in the response to HFS. We observed a pronounced increase in striatal levels of AEA, but not the other major endogenous cannabinoid 2-arachidonoylglycerol (2-AG), during the postnatal period characterized by the switch from LTP to LTD. Furthermore, application of synthetic AEA during HFS in field recordings of slices from P12-P14 rats allowed for induction of LTD whereas blocking the CB1 receptor during HFS in animals P16 -P34 resulted in expression of LTP. However, blocking 2-AG synthesis with the DAG-lipase inhibitor tetrahydrolipstatin did not alter HFSinduced striatal LTD. In addition, synaptic depression produced by a synthetic CB1 agonist was similar across development. Together, these findings suggest that the robust developmental increase in striatal AEA may be the key factor in the emergence of HFS-induced striatal LTD.

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Selective involvement of mGlu1 receptors in corticostriatal LTD

Cited by 103 publications

References 48 publications

mGluR5 Antagonist MPEP Reduces Ethanol-Seeking and Relapse Behavior

mGluR5 Antagonist MPEP Reduces Ethanol-Seeking and Relapse Behavior

Combined Activation of L-Type Ca2+ Channels and Synaptic Transmission Is Sufficient to Induce Striatal Long-Term Depression

Anandamide Regulates Postnatal Development of Long-Term Synaptic Plasticity in the Rat Dorsolateral Striatum

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