title: Reduced dopamine and glutamate neurotransmission in the nucleus accumbens of quinpirole-sensitized rats hints at inhibitory D2 autoreceptor function.
abstract: Dopamine from the ventral tegmental area and glutamate from several brain nuclei converge in the nucleus accumbens (NAc) to drive motivated behaviors. Repeated activation of D2 receptors with quinpirole (QNP) induces locomotor sensitization and compulsive behaviors, but the mechanisms are unknown. In this study, in vivo microdialysis and fast scan cyclic voltammetry in adult anesthetized rats were used to investigate the effect of repeated QNP on dopamine and glutamate neurotransmission within the NAc. Following eight injections of QNP, a significant decrease in phasic and tonic dopamine release was observed in rats that displayed locomotor sensitization. Either a systemic injection or the infusion of QNP into the NAc decreased dopamine release, and the extent of this effect was similar in QNP-sensitized and control rats, indicating that inhibitory D2 autoreceptor function is maintained despite repeated activation of D2 receptors and decreased dopamine extracellular levels. Basal extracellular levels of glutamate in the NAc were also significantly lower in QNP-treated rats than in controls. Moreover, the increase in NAc glutamate release induced by direct stimulation of medial prefrontal cortex was significantly lower in QNP-sensitized rats. Together, these results indicate that repeated activation of D2 receptors disconnects NAc from medial prefrontal cortex and ventral tegmental area. Repeated administration of the dopamine D2 receptor agonist quinpirole (QNP) induces locomotor sensitization. We found that the NAc of QNP-sensitized rats has reduced glutamate levels coming from prefrontal cortex together with a decreased phasic and tonic dopamine neurotransmission but a conserved presynaptic D2 receptor function. We suggest that locomotor sensitization is because of increased affinity state of D2 post-synaptic receptors.
authors.affiliation: Millennium Science Nucleus in Stress and Addiction, Pontificia Universidad Católica de Chile, Santiago, Chile.|Department of Cellular and Molecular Biology, Faculty of Biological Science, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Angélica P
authors.initials: AP
authors.lastname: Escobar
authors.affiliation: Millennium Science Nucleus in Stress and Addiction, Pontificia Universidad Católica de Chile, Santiago, Chile.|Department of Cellular and Molecular Biology, Faculty of Biological Science, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Francisca A
authors.initials: FA
authors.lastname: Cornejo
authors.affiliation: Millennium Science Nucleus in Stress and Addiction, Pontificia Universidad Católica de Chile, Santiago, Chile.|Department of Cellular and Molecular Biology, Faculty of Biological Science, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Olivares-Costa
authors.affiliation: Millennium Science Nucleus in Stress and Addiction, Pontificia Universidad Católica de Chile, Santiago, Chile.|Department of Cellular and Molecular Biology, Faculty of Biological Science, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Marcela
authors.initials: M
authors.lastname: González
authors.affiliation: Millennium Science Nucleus in Stress and Addiction, Pontificia Universidad Católica de Chile, Santiago, Chile.|Department of Pharmacy, Faculty of Chemistry, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: José A
authors.initials: JA
authors.lastname: Fuentealba
authors.affiliation: Millennium Science Nucleus in Stress and Addiction, Pontificia Universidad Católica de Chile, Santiago, Chile.|Department of Cellular and Molecular Biology, Faculty of Biological Science, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Katia
authors.initials: K
authors.lastname: Gysling
authors.affiliation: Department Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: España
authors.affiliation: Millennium Science Nucleus in Stress and Addiction, Pontificia Universidad Católica de Chile, Santiago, Chile.|Department of Cellular and Molecular Biology, Faculty of Biological Science, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: María E
authors.initials: ME
authors.lastname: Andrés
mesh_terms: D000818:Animals; D017660:Autoreceptors / Q000378:metabolism*; D059333:Central Nervous System Sensitization / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis; D009043:Motor Activity / Q000502:physiology; D009714:Nucleus Accumbens / Q000378:metabolism*; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D017660:Autoreceptors; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D018698:Glutamic Acid; D004298:Dopamine
keywords: dopamine; fast scan cyclic voltammetry; glutamate; microdialysis; nucleus accumbens; quinpirole