title: Decreased CB receptor binding and cannabinoid signaling in three brain regions of a rat model of schizophrenia.
abstract: Schizophrenia is a serious mental health disorder characterized by several behavioral and biochemicel abnormalities. In a previous study we have shown that mu-opioid (MOP) receptor signaling is impaired in specific brain regions of our three-hit animal model of schizophrenia. Since the cannabinoid system is significantly influenced in schizophrenic patients, in the present work we investigated cannabinoid (CB) receptor binding and G-protein activation in cortical, subcortical and cerebellar regions of control and 'schizophrenic' rats. Cannabinoid agonist (WIN-55,212-2 mesylate) mediated G-protein activation was consistently decreased in all areas tested, and the difference was extremely significant in membranes prepared from the cerebellum. Interestingly, the cerebellar activity of WIN-55,212-2 stimulated G-proteins was substantially higher than those of cerebral cortex and subcortical region in control animals, indicating a primordial role of the cannabinoid system in the cerebellum. At the level of radioligand binding, the affinities of the CB receptors were also markedly decreased in the model animals. Capacity of the [3H]WIN-55,212-2 binding was only higher in the cerebellum of 'schizophrenic' model rats. Taken together, in all three brain areas of model rats both cannabinoid receptor binding and cannabinoid agonist-mediated G-protein activation were regularly decreased. Our results revealed that besides the opioids, the endocannabinoid - cannabis receptor system also shows impairment in our rat model, increasing its face validity and translational utility.
authors.affiliation: Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, H-6726 Szeged, Temesvári krt. 62., Hungary(1).
authors.forename: Edina
authors.initials: E
authors.lastname: Szűcs
authors.affiliation: Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, H-6726 Szeged, Temesvári krt. 62., Hungary(1).
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Dvorácskó
authors.affiliation: Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, H-6726 Szeged, Temesvári krt. 62., Hungary(1).
authors.forename: Csaba
authors.initials: C
authors.lastname: Tömböly
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Szeged, H-6720 Szeged, Dóm tér 10., Hungary.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Büki
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Szeged, H-6720 Szeged, Dóm tér 10., Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Kékesi
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Szeged, H-6720 Szeged, Dóm tér 10., Hungary.
authors.forename: Gyöngyi
authors.initials: G
authors.lastname: Horváth
authors.affiliation: Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, H-6726 Szeged, Temesvári krt. 62., Hungary(1). Electronic address: benyhe@brc.hu.
authors.forename: Sándor
authors.initials: S
authors.lastname: Benyhe
mesh_terms: D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D063388:Endocannabinoids / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D011869:Radioligand Assay; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D063388:Endocannabinoids; D009025:Morpholines; D009281:Naphthalenes; D043882:Receptors, Cannabinoid; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
keywords: Cannabinoid receptors; G-protein activation; Radioligand binding; Schizophrenia animal model; WIN-55,212-2 mesylate; [(35)S]GTPγS binding