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The α2C-adrenoceptor antagonist JP-1302 controls behavioral parameters, tyrosine hydroxylase activity and receptor expression in a rat model of ketamine-induced schizophrenia-like deficits

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dc.contributor.authorAKAKIN, DİLEK
dc.contributor.authorGÖREN, MEHMET ZAFER
dc.contributor.authorsTekin N., Karamahmutoğlu T. E. , Aykaç A., AKAKIN D., GÖREN M. Z.
dc.date.accessioned2022-12-22T12:34:27Z
dc.date.available2022-12-22T12:34:27Z
dc.date.issued2022-11-01
dc.description.abstract© 2022Schizophrenia is a chronic disabling disease affecting 1 % of the population. Current antipsychotics have limited efficacy in mitigating the severity of the symptoms of the disease. Therefore, searching for new therapeutic targets is essential. Previous studies have shown that α2C-adrenoceptor antagonists may have antipsychotic and pro-cognitive effects. Therefore, the current study evaluates the behavioral and neurochemical effects of JP-1302, a selective α2C-adrenoceptor antagonist, in a model of schizophrenia-like deficits induced by sub-chronic ketamine (KET) administration. Here, we administered ketamine (25 mg/kg, i.p.) to male and female Wistar rats for eight consecutive days. On the last two days of ketamine administration, rats were pretreated with either JP-1302 (1-3-10 μmol/kg, i.p.), chlorpromazine (0.1 mg/kg, i.p.), or saline, and the behavioral tests were performed. Behaviors related to positive (locomotor activity), negative (social interaction), and cognitive (novel object recognition) symptoms of schizophrenia were assessed. Glutamate, glutamine, GABA levels, and α2C-adrenoceptor expression were measured in the frontal cortex and the hippocampus. Tyrosine hydroxylase immunocytochemical reactivity was also shown in the midbrain regions. Sub-chronic ketamine administration increased locomotor activity and produced robust social interaction and object recognition deficits, and JP-1302 significantly ameliorated ketamine-induced cognitive deficits. Ketamine induced a hyperdopaminergic activity in the striatum, which was reversed by the treatment with JP-1302. Also, the α2C-adrenoceptor expression was higher in the frontal cortex and hippocampus in the ketamine-treated rats. Our findings confirm that α2C-adrenoceptor antagonism may be a potential drug target for treating cognitive disorders related to schizophrenia.
dc.identifier.citationTekin N., Karamahmutoğlu T. E. , Aykaç A., AKAKIN D., GÖREN M. Z. , "The α2C-adrenoceptor antagonist JP-1302 controls behavioral parameters, tyrosine hydroxylase activity and receptor expression in a rat model of ketamine-induced schizophrenia-like deficits", Pharmacology Biochemistry and Behavior, cilt.221, 2022
dc.identifier.doi10.1016/j.pbb.2022.173490
dc.identifier.endpage9
dc.identifier.issn0091-3057
dc.identifier.startpage1
dc.identifier.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85142394650&origin=inward
dc.identifier.urihttps://hdl.handle.net/11424/283807
dc.identifier.volume221
dc.language.isoeng
dc.relation.ispartofPharmacology Biochemistry and Behavior
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectTemel Eczacılık Bilimleri
dc.subjectEczacılık
dc.subjectMeslek Bilimleri
dc.subjectFarmasötik Toksikoloji
dc.subjectSosyal ve Beşeri Bilimler
dc.subjectPsikoloji
dc.subjectDavranış Bilimleri
dc.subjectYaşam Bilimleri
dc.subjectMoleküler Biyoloji ve Genetik
dc.subjectSitogenetik
dc.subjectSağlık Bilimleri
dc.subjectTemel Bilimler
dc.subjectBasic Pharmaceutics Sciences
dc.subjectPharmacology and Therapeutics
dc.subjectProfessional Sciences
dc.subjectPharmaceutical Toxicology
dc.subjectSocial Sciences and Humanities
dc.subjectPsychology
dc.subjectBehavioural Sciences
dc.subjectLife Sciences
dc.subjectMolecular Biology and Genetics
dc.subjectCytogenetic
dc.subjectHealth Sciences
dc.subjectNatural Sciences
dc.subjectTemel Bilimler (SCI)
dc.subjectYaşam Bilimleri (LIFE)
dc.subjectSinirbilim ve Davranış
dc.subjectFarmakoloji ve Toksikoloji
dc.subjectPSİKOLOJİ, BİYOLOJİK
dc.subjectDAVRANIŞ BİLİMLERİ
dc.subjectFARMAKOLOJİ VE ECZACILIK
dc.subjectTOKSİKOLOJİ
dc.subjectBİYOKİMYA VE MOLEKÜLER BİYOLOJİ
dc.subjectNatural Sciences (SCI)
dc.subjectLife Sciences (LIFE)
dc.subjectPSYCHOLOGY
dc.subjectNEUROSCIENCE & BEHAVIOR
dc.subjectPHARMACOLOGY & TOXICOLOGY
dc.subjectMOLECULAR BIOLOGY & GENETICS
dc.subjectPSYCHOLOGY, BIOLOGICAL
dc.subjectBEHAVIORAL SCIENCES
dc.subjectPHARMACOLOGY & PHARMACY
dc.subjectTOXICOLOGY
dc.subjectBIOCHEMISTRY & MOLECULAR BIOLOGY
dc.subjectBiyokimya
dc.subjectToksikoloji
dc.subjectFarmakoloji
dc.subjectKlinik Biyokimya
dc.subjectBiyolojik Psikiyatri
dc.subjectDavranışsal Sinirbilim
dc.subjectBiochemistry
dc.subjectToxicology
dc.subjectPharmacology
dc.subjectClinical Biochemistry
dc.subjectBiological Psychiatry
dc.subjectBehavioral Neuroscience
dc.subjectHPLC
dc.subjectNovel object recognition
dc.subjectSchizophrenia
dc.subjectWestern-blotting
dc.titleThe α2C-adrenoceptor antagonist JP-1302 controls behavioral parameters, tyrosine hydroxylase activity and receptor expression in a rat model of ketamine-induced schizophrenia-like deficits
dc.typearticle
dspace.entity.typePublication
local.avesis.id91732124-bdc1-49df-94ba-38e12e6d6add
local.indexed.atPUBMED
local.indexed.atSCOPUS
relation.isAuthorOfPublicationc97c0ebf-ffce-4b27-a933-941a53767b0d
relation.isAuthorOfPublicationf91c1cf5-3919-48eb-a772-35abafdc304e
relation.isAuthorOfPublication.latestForDiscoveryc97c0ebf-ffce-4b27-a933-941a53767b0d

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