The effects of the mGluR5 receptor antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP) on behavioural responses to nicotine

Tronci, Valeria; Vronskaya, Svetlana; Montgomery, Nicholas; Mura, D.; Balfour, David J.K.

doi:10.1007/s00213-010-1868-x

Cited by 32 publications

(45 citation statements)

References 30 publications

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“…The results suggested that MPEP may not selectively suppress the primary reinforcing properties of nicotine. It seems unlikely that the reductions in responding on the active and inactive levers in these experiments reflected a generalised suppression of behaviour since, as previously reported (Tessari et al 2004), pretreatment with MPEP did not reduce spontaneous locomotor activity (Tronci et al 2010). Additionally, MPEP pretreatment does not diminish operant responding for a food reward (Bespalov et al 2005;Liechti and Markou 2007a;Tronci et al 2010).…”

Section: The Role Of Contextual Stimuli In Psychopharmacological Respsupporting

confidence: 51%

“…Pretreatment with MPEP not only suppressed active lever presses but also suppressed responding on the inactive lever. This was also true for the effects of MPEP on nicotine self-administration (Tronci et al 2010). The results suggested that MPEP may not selectively suppress the primary reinforcing properties of nicotine.…”

Section: The Role Of Contextual Stimuli In Psychopharmacological Respmentioning

confidence: 75%

“…The DA projections from the ventral tegmental area to the nucleus accumbens are also thought to mediate the stimulant effects of nicotine on spontaneous locomotor activity (Clarke et al 1988; (Tessari et al 2004;Tronci et al 2010). This conundrum may be explained by the fact that DA can be released from mesolimbic DA neurones into two compartments -the synaptic cleft formed at tight synaptic junctions and the extracellular space which lies between the fibres that project into the accumbens.…”

Section: The Role Of Mglur5 Receptors In the Neural Responses To Nicomentioning

confidence: 99%

“…The administration of mGluR5 antagonists to animals trained to respond for nicotine in an intravenous self-administration paradigm has consistently been shown to result in a dose-dependent attenuation of nicotine-seeking behaviour (Kenny et al 2003;Paterson et al 2003;Tessari et al 2004;Liechti and Markou 2007a;Palmatier et al 2007;Tronci et al 2010). Moreover, pretreatment with the mGluR5 antagonist, MPEP, is reported to decrease the break point for nicotine in a progressive ratio schedule of reinforcement (Paterson and Markou 2005).…”

Section: The Role Of Mglur5 Receptors In Models Of Nicotine Dependencementioning

confidence: 99%

“…These compounds also inhibit the self-administration of other drugs of dependence such as cocaine 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 11 responding for drug rewards (Chiamulera et al 2001;Paterson et al 2003;Tessari et al 2004;Osborne and Olive 2008;Tronci et al 2010). In these studies, however, responding was generally studied using a fixed ratio paradigm.…”

Section: The Role Of Mglur5 Receptors In Models Of Nicotine Dependencementioning

confidence: 99%

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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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Section: The Role Of Contextual Stimuli In Psychopharmacological Respsupporting

confidence: 51%

Section: The Role Of Contextual Stimuli In Psychopharmacological Respmentioning

confidence: 75%

Section: The Role Of Mglur5 Receptors In the Neural Responses To Nicomentioning

confidence: 99%

Section: The Role Of Mglur5 Receptors In Models Of Nicotine Dependencementioning

confidence: 99%

Section: The Role Of Mglur5 Receptors In Models Of Nicotine Dependencementioning

confidence: 99%

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Metabotropic glutamate receptor 5 as a potential target for smoking cessation

2016

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Metabotropic glutamate receptors and drug addiction

Cleva

2012

WIREs Membr Transp Signal

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Historically, brain catecholamine systems have been the primary focus of studies examining the neural substrates of drug addiction. In the past two decades, however, a wealth of evidence has accumulated indicating a pivotal role for glutamatergic neurotransmission in mediating addictive behaviors as well as long-term neuroplasticity associated with chronic drug use. As a result, there has been increased interest in developing glutamate-based therapies for the treatment of addictive disorders. Metabotropic glutamate (mGlu) receptors are classified into subcategories designated as Group I (mGlu1 and mGlu5), Group II (mGlu2 and mGlu3), and Group III (mGlu4, mGlu6, mGlu7, and mGlu8), and have received a great deal of attention due to their mediation of slower modulatory excitatory neurotransmission. Pharmacological ligands targeting these receptors have demonstrated reduced incidences of excitotoxicity or severe adverse side effects as compared to those targeting ionotropic glutamate (iGlu) receptors. Behavioral genetic and pharmacological studies have explored the role of individual mGlu receptor subtypes in regulating various addiction-related behaviours and several mGlu receptor ligands have been the subject of clinical testing for other medical conditions.

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The Role of Mesoaccumbens Dopamine in Nicotine Dependence

Balfour

2015

The Neuropharmacology of Nicotine Dependence

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There is abundant evidence that the dopamine (DA) neurons that project to the nucleus accumbens play a central role in neurobiological mechanisms underpinning drug dependence. This chapter considers the ways in which these projections facilitate the addiction to nicotine and tobacco. It focuses on the complimentary roles of the two principal subdivisions of the nucleus accumbens, the accumbal core and shell, in the acquisition and maintenance of nicotine-seeking behavior. The ways in which tonic and phasic firing of the neurons contributes to the ways in which the accumbens mediate the behavioral responses to nicotine are also considered. Experimental studies suggest that nicotine has relatively weak addictive properties which are insufficient to explain the powerful addictive properties of tobacco smoke. This chapter discusses hypotheses that seek to explain this conundrum. They implicate both discrete sensory stimuli closely paired with the delivery of tobacco smoke and contextual stimuli habitually associated with the delivery of the drug. The mechanisms by which each type of stimulus influence tobacco dependence are hypothesized to depend upon the increased DA release and overflow, respectively, in the two subdivisions of the accumbens. It is suggested that a majority of pharmacotherapies for tobacco dependence are not more successful because they fail to address this important aspect of the dependence.

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The effects of the mGluR5 receptor antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP) on behavioural responses to nicotine

Cited by 32 publications

References 30 publications

Metabotropic glutamate receptor 5 as a potential target for smoking cessation

Metabotropic glutamate receptor 5 as a potential target for smoking cessation

Metabotropic glutamate receptors and drug addiction

The Role of Mesoaccumbens Dopamine in Nicotine Dependence

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