Anxiolytic and antidepressant-like activities of the novel and potent non-imidazole histamine H3 receptor antagonist ST-1283

نویسندگان

  • Amine Bahi
  • Johannes Stephan Schwed
  • Miriam Walter
  • Holger Stark
  • Bassem Sadek
چکیده

Previous studies have suggested a potential link between histamine H₃ receptors (H₃R) signaling and anxiolytic-like and antidepressant-like effects. The aim of this study was to investigate the acute effects of ST-1283, a novel H₃R antagonist, on anxiety-related and depression-related behaviors in comparison with those of diazepam and fluoxetine. The effects of ST-1283 were evaluated using the elevated plus maze test, open field test, marbles burying test, tail suspension test, novelty suppressed feeding test, and forced swim test in male C57BL/6 mice. The results showed that, like diazepam, ST-1283 (7.5 mg/kg) significantly modified all the parameters observed in the elevated plus maze test. In addition, ST-1283 significantly increased the amount of time spent in the center of the arena without altering general motor activity in the open field test. In the same vein, ST-1283 reduced the number of buried marbles as well as time spent digging in the marbles burying test. The tail suspension test and forced swim test showed that ST-1283 was able to reduce immobility time, like the recognized antidepressant drug fluoxetine. In the novelty suppressed feeding test, treatment with ST-1283 decreased latency to feed with no effect on food intake in the home cage. Importantly, pretreatment with the H₃R agonist R-α-methylhistamine abrogated the anxiolytic and antidepressant effects of ST-1283. Taken together, the present series of studies demonstrates the novel effects of this newly synthesized H₃R antagonist in a number of preclinical models of psychiatric disorders and highlights the histaminergic system as a potential therapeutic target for the treatment of anxiety-related and depression-related disorders.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Identification and Characterization of ZEL-H16 as a Novel Agonist of the Histamine H3 Receptor

The histamine H3 receptor (H3R) has been recognized as a promising target for the treatment of various central and peripheral nervous system diseases. In this study, a non-imidazole compound, ZEL-H16, was identified as a novel histamine H3 receptor agonist. ZEL-H16 was found to bind to human H3R with a Ki value of approximately 2.07 nM and 4.36 nM to rat H3R. Further characterization indicated ...

متن کامل

Pharmacological properties of ABT-239 [4-(2-{2-[(2R)-2-Methylpyrrolidinyl]ethyl}-benzofuran-5-yl)benzonitrile]: I. Potent and selective histamine H3 receptor antagonist with drug-like properties.

Histamine H3 receptor antagonists are being developed to treat a variety of neurological and cognitive disorders that may be ameliorated by enhancement of central neurotransmitter release. Here, we present the in vitro pharmacological and in vivo pharmacokinetic profiles for the nonimidazole, benzofuran ligand ABT-239 [4-(2-{2-[(2R)-2-methylpyrrolidinyl]ethyl}-benzofuran-5-yl)benzonitrile] and ...

متن کامل

Intracerebroventricular Injection of Histamine Induces State-Dependency through H1 Receptors

The aim of the present study was to investigate whether and by which mechanism; histamine can induce state-dependent retrieval of passive avoidance task. The pre-training or pre-test intracerebroventricular (i.c.v.) injection of histamine (20µg/mouse) impaired retrieval, when it was tested 24 h later. In the animals, which retrieval was impaired due to histamine pre-training administration, pre...

متن کامل

The role of central endogenous histamine and H1, H2 and H3 receptors on food intake in broiler chickens

The role of endogenous histamine and H1, H2 and H3 central receptors on food intake in broiler chickenswas investigated. For this purpose, a probe was used to manipulate the concentration of endogenoushistamine by intracerebroventricular (ICV) injection of thioperamide, an H3 receptor antagonist, and R-α-methylhistamine, an H3 receptor agonist and subsequently the effects of brain histaminergic...

متن کامل

میانکنش سیستم هیستامینرژیک هیپوکامپ پشتی و اپیوئیدرژیک سپتوم میانی بر رفتارهای شبه اضطرابی

Septohippocampal system plays an important role in regulating fear and anxiety behaviors. In this study, the effects of histamine injected into the dorsal hippocampus and opioidergic agents into medial septum on the anxiety-like behaviors in rats were analyzed, using the Elevated Plus-Maze (EPM) test. Injection of 1 and 5 μg/rat histamine into dorsal hippocampus had no effect on anxiety-like...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 8  شماره 

صفحات  -

تاریخ انتشار 2014