GPR88 in A 2A receptor-expressing neurons modulates locomotor response to dopamine agonists but not sensorimotor gating.

Autor: Meirsman AC; Département de Médecine Translationnelle et Neurogénétique, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U-964, CNRS UMR-7104, Université de Strasbourg, Illkirch, France.; Neuroscience Paris Seine, Institut de Biologie Paris Seine, CNRS UMR 8246/INSERM U1130/Université Pierre et Marie Currie, Paris, France., de Kerchove d'Exaerde A; Laboratory of Neurophysiology, ULB Neuroscience Institute, Université Libre de Bruxelles, Bruxelles, Belgium., Kieffer BL; Département de Médecine Translationnelle et Neurogénétique, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U-964, CNRS UMR-7104, Université de Strasbourg, Illkirch, France.; Department of Psychiatry, Faculty of Medicine, Douglas Research Center, McGill University, Montréal, QC, Canada., Ouagazzal AM; Département de Médecine Translationnelle et Neurogénétique, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U-964, CNRS UMR-7104, Université de Strasbourg, Illkirch, France.; Laboratoire de Neurosciences Cognitives, AMU-CNRS UMR-7291, Aix-Marseille Université, Marseille, France.
Jazyk: angličtina
Zdroj: The European journal of neuroscience [Eur J Neurosci] 2017 Aug; Vol. 46 (4), pp. 2026-2034. Date of Electronic Publication: 2017 Aug 02.
DOI: 10.1111/ejn.13646
Abstrakt: The orphan receptor, GPR88, is emerging as a key player in the pathophysiology of several neuropsychiatric diseases, including psychotic disorders. Knockout (KO) mice lacking GPR88 throughout the brain exhibit many abnormalities relevant to schizophrenia including locomotor hyperactivity, behavioural hypersensitivity to dopaminergic psychostimulants and deficient sensorimotor gating. Here, we used conditional knockout (cKO) mice lacking GPR88 selectively in striatal medium spiny neurons expressing A 2A receptor to determine neuronal circuits underlying these phenotypes. We first studied locomotor responses of A 2 A R-Gpr88 KO mice and their control littermates to psychotomimetic, amphetamine, and to selective D1 and D2 receptor agonists, SKF-81297 and quinpirole, respectively. To assess sensorimotor gating performance, mice were submitted to acoustic and visual prepulse inhibition (PPI) paradigms. Total knockout GPR88 mice were also studied for comparison. Like total GPR88 KO mice, A 2 A R-Gpr88 KO mice displayed a heightened sensitivity to locomotor stimulant effects of amphetamine and SKF-81297. They also exhibited enhanced locomotor activity to quinpirole, which tended to suppress locomotion in control mice. By contrast, they had normal acoustic and visual PPI, unlike total GPR88 KO mice that show impairments across different sensory modalities. Finally, none of the genetic manipulations altered central auditory temporal processing assessed by gap-PPI. Together, these findings support the role of GPR88 in the pathophysiology of schizophrenia and show that GPR88 in A 2A receptor-expressing neurons modulates psychomotor behaviour but not sensorimotor gating.
(© 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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