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Reduced dopamine and glutamate neurotransmission in the nucleus accumbens of quinpirole-sensitized rats hints at inhibitory D2 autoreceptor function
Journal article   Open access   Peer reviewed

Reduced dopamine and glutamate neurotransmission in the nucleus accumbens of quinpirole-sensitized rats hints at inhibitory D2 autoreceptor function

Angélica P Escobar, Francisca A Cornejo, Montserrat Olivares-Costa, Marcela González, José A Fuentealba, Katia Gysling, Rodrigo A España and María E Andrés
Journal of neurochemistry, v 134(6), pp 1081-1090
Sep 2015
DOI: https://doi.org/10.1111/jnc.13209
PMID: 26112331
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1007/s11390-017-1782-3View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open

Abstract

Animals Autoreceptors - metabolism Central Nervous System Sensitization - physiology Dopamine - metabolism Dopamine Agonists - pharmacology Female Glutamic Acid - metabolism Male Mice Mice, Inbred C57BL Microdialysis Motor Activity - physiology Nucleus Accumbens - metabolism Quinpirole - pharmacology Rats Rats, Sprague-Dawley Receptors, Dopamine D2 - metabolism Synaptic Transmission - physiology
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.

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Collaboration types
Domestic collaboration
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Web of Science research areas
Biochemistry & Molecular Biology
Neurosciences
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