title: The mGluR5 antagonist MPEP elevates accumbal dopamine and glycine levels; interaction with strychnine-sensitive glycine receptors.
abstract: Studies have indicated that the metabotropic glutamate receptor 5 (mGluR5) antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP) decreases ethanol self-administration, and the same receptor type was also suggested to be involved in the mechanism of action of the anti-craving substance acamprosate. Our previous research suggested that glycine receptors (GlyRs) in the nucleus accumbens (nAc) play a major part in mediating the dopamine-elevating properties of ethanol and are highly involved in the ethanol intake-reducing effect of acamprosate. The aim of this study was to examine if modulation of nAc dopamine via mGluR5 antagonism or GlyR agonism is a linked or separated phenomena. The extracellular levels of dopamine as well as of the GlyR ligands, glycine, taurine and β-alanine were measured in the nAc by means of microdialysis after local perfusion of MPEP (100 or 500 µM) with or without pre-treatment with strychnine. MPEP increased dopamine levels, an effect that was blocked by pre-treatment with strychnine. In addition, the higher MPEP concentration increased glycine output, whereas no alterations of taurine or β-alanine were observed. These results indicate a relationship between the glutamatergic and glycinergic transmitter systems in regulating dopamine output, possibly via alteration of extracellular glycine levels. Taken together with our previous data demonstrating the importance of accumbal GlyRs both in ethanol-induced elevation of nAc dopamine and in ethanol consumption, it is plausible that the effects of MPEP treatment, on dopamine output and on ethanol intake, may be mediated via interaction with the same neuronal circuitry that previously has been demonstrated for ethanol, taurine and acamprosate.
authors.affiliation: Addiction Biology Unit, Institute of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Sweden. peipei.chau@neuro.gu.se
authors.forename: PeiPei
authors.initials: P
authors.lastname: Chau
authors.forename: Bo
authors.initials: B
authors.lastname: Söderpalm
authors.forename: Mia
authors.initials: M
authors.lastname: Ericson
mesh_terms: D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005998:Glycine / Q000378:metabolism*; D018684:Glycine Agents / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D018009:Receptors, Glycine / Q000187:drug effects* / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000502:physiology*; D013331:Strychnine / Q000494:pharmacology*; D013654:Taurine / Q000378:metabolism; D015091:beta-Alanine / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018684:Glycine Agents; C578937:Grm5 protein, rat; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018009:Receptors, Glycine; D018094:Receptors, Metabotropic Glutamate; D015091:beta-Alanine; D013654:Taurine; C121465:6-methyl-2-(phenylethynyl)pyridine; D013331:Strychnine; D005998:Glycine; D004298:Dopamine