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

Autor: Nurdan Tekin, Tuğba Eryiğit Karamahmutoğlu, Aslı Aykaç, Dilek Akakın, Mehmet Zafer Gören
Přispěvatelé: Tekin N., Karamahmutoğlu T. E. , Aykaç A., AKAKIN D., GÖREN M. Z.
Rok vydání: 2022
Předmět:
Social Sciences and Humanities
NEUROSCIENCE & BEHAVIOR
Pharmaceutical Toxicology
TOKSİKOLOJİ
Clinical Biochemistry
Temel Bilimler (SCI)
Biyolojik Psikiyatri
Sağlık Bilimleri
Toxicology
Biochemistry
Behavioral Neuroscience
BİYOKİMYA VE MOLEKÜLER BİYOLOJİ
Biyokimya
FARMAKOLOJİ VE ECZACILIK
Psychology
PHARMACOLOGY & PHARMACY
PHARMACOLOGY & TOXICOLOGY
Temel Bilimler
Basic Pharmaceutics Sciences
Life Sciences
Davranışsal Sinirbilim
Behavioural Sciences
Toksikoloji
Farmasötik Toksikoloji
MOLECULAR BIOLOGY & GENETICS
Davranış Bilimleri
Farmakoloji ve Toksikoloji
Natural Sciences (SCI)
Sinirbilim ve Davranış
PSİKOLOJİ
BİYOLOJİK
Natural Sciences
BIOCHEMISTRY & MOLECULAR BIOLOGY
Sitogenetik
BEHAVIORAL SCIENCES
Farmakoloji
Novel object recognition
Life Sciences (LIFE)
Molecular Biology and Genetics
Meslek Bilimleri
Yaşam Bilimleri
Health Sciences
Professional Sciences
Sosyal ve Beşeri Bilimler
Cytogenetic
PSYCHOLOGY
BIOLOGICAL
Eczacılık
Moleküler Biyoloji ve Genetik
Biological Psychiatry
Pharmacology
Pharmacology and Therapeutics
Klinik Biyokimya
Psikoloji
Temel Eczacılık Bilimleri
Yaşam Bilimleri (LIFE)
Western-blotting
Schizophrenia
HPLC
DAVRANIŞ BİLİMLERİ
Zdroj: Pharmacology Biochemistry and Behavior. 221:173490
ISSN: 0091-3057
Popis: © 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.
Databáze: OpenAIRE
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