title: mGlu5 receptor antagonist blocks bromocriptine-induced conditioned place preference in bilateral mesolimbic-lesioned rat.
abstract: Dopamine dysregulation syndrome (DDS) has been attributed to both dopamine replacement therapies (DRT) and the mesencephalic dopaminergic lesion. The DRT reinforcement effect is due to its action on the reward system, particularly on the nucleus accumbens (NAc). This nucleus receives two major projections, a glutamatergic from the prefrontal cortex and a dopaminergic from the posterior ventral tegmental area (pVTA). The latter modulate the former within the NAc. pVTA has been demonstrated to be implicated in the motivational effect of bromocriptine (dopamine 2 receptor (D2R) agonist) in bilateral pVTA-lesioned animals. Therefore the potential implication of the metabotropic glutamate receptor 5 (mGluR5) antagonist (MTEP: 3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine) on bromocriptine-induced conditioned place preference (CPP) was explored. Results showed that the administration of the MTEP blocked completely the bromocriptine-induced CPP in bilateral pVTA-lesioned rats. Both the CPP acquisition and expression were abolished. These effects are due, at least to an increase of the glutamate concentration and that of mGlu5 receptor expression in the NAc shell of the pVTA-lesioned animals. Altogether these data demonstrated the importance of the mGlu5 receptor in the bromocriptine induced-reinforcement and that DDS is probably due to DRT effect on this glutamate receptor.
authors.affiliation: Clermont Université, Université d'Auvergne, EA7280, Laboratoire de Neuropsychopharmacologie des systèmes dopaminergiques sous corticaux, Clermont-Ferrand, France.
authors.forename: Omar
authors.initials: O
authors.lastname: Ouachikh
authors.affiliation: Clermont Université, Université d'Auvergne, EA7280, Laboratoire de Neuropsychopharmacologie des systèmes dopaminergiques sous corticaux, Clermont-Ferrand, France; CHU Clermont-Ferrand, Service de Neurologie, 63000 Clermont-Ferrand, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Chassain
authors.affiliation: 2NMR platform "AgroResonance", UR370 Qualité des produits animaux (QuaPA), INRA-Centre, Auvergne-Rhône-Alpes, 63122 Saint-Genès Champanelle, France.
authors.forename: Guilhem
authors.initials: G
authors.lastname: Pagès
authors.affiliation: Clermont Université, Université d'Auvergne, EA7280, Laboratoire de Neuropsychopharmacologie des systèmes dopaminergiques sous corticaux, Clermont-Ferrand, France; CHU Clermont-Ferrand, Service de Neurologie, 63000 Clermont-Ferrand, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Durif
authors.affiliation: Clermont Université, Université d'Auvergne, EA7280, Laboratoire de Neuropsychopharmacologie des systèmes dopaminergiques sous corticaux, Clermont-Ferrand, France. Electronic address: azhafidi@univ-bpclermont.fr.
authors.forename: Aziz
authors.initials: A
authors.lastname: Hafidi
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001971:Bromocriptine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D003891:Desipramine / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects; D016627:Oxidopamine / Q000633:toxicity; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*; D012054:Reinforcement, Psychology; D013844:Thiazoles / Q000494:pharmacology*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000293:injuries*
chemical_list: C472365:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; D018663:Adrenergic Agents; D018759:Adrenergic Uptake Inhibitors; D000978:Antiparkinson Agents; D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D013844:Thiazoles; D001971:Bromocriptine; D016627:Oxidopamine; D003891:Desipramine
keywords: 6-OHDA; Conditioned place preference; Parkinson; Reward