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Dernière publication 01/04/2016

SB 334867- a selective orexin receptor type 1 antagonist- elevates seizure thres

AIM: Orexins A and B are hypothalamic neuropeptides involved in a number of physiological and behavioral processes. They work via OX1 and OX2...

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    [title] => SB 334867- a selective orexin receptor type 1 antagonist- elevates seizure thres
    [paragraph] => SB 334867, a selective orexin receptor type 1 antagonist, elevates seizure threshold in mice
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Authors
Socała K, Szuster-Ciesielska A, Wlaź P

 Lab
Department of Animal Physiology, Institute of Biology and Biochemistry, Maria Curie-Skłodowska University, Lublin, Poland.
Journal
Life Sci. 
Abstract
AIM:

 Orexins A and B are hypothalamic neuropeptides involved in a number of physiological and behavioral processes. They work via OX1 and OX2 receptors. Recent studies revealed that orexins may be implicated in seizure activity. Therefore, the present study was undertaken to evaluate the influence of SB 334867 (a selective OX1 receptor antagonist) and EMPA (a selective OX2 receptor antagonist) on the seizure thresholds in mice. We also aimed to determine the changes of orexin A level following different types of seizures.

 MAIN METHODS:

 The intravenous pentylenetetrazole (i.v. PTZ) seizure test, the maximal electroshock seizure threshold (MEST) test and the 6Hz seizure test were used in the present study. Brain orexin A level was determined via enzyme-linked immunoassay (ELISA).

 KEY FINDINGS:

 SB 334867 did not affect the seizure threshold for myoclonic twitches and tonic seizures in the i.v. PTZ seizure test. This compound, however, significantly raised the threshold for the PTZ-induced clonic seizures, for tonic hindlimb extension in the MEST test as well as for psychomotor seizures induced by 6Hz stimulation. In comparison, EMPA did not alter the seizure thresholds in the i.v. PTZ test. Both EMPA and SB 334867 did not affect motor coordination and muscular strength. ELISA showed the increase of total brain orexin A level following different types of seizures.

 SIGNIFICANCE:

 Our results provide further evidence for the role of orexins in seizure activity and suggest that pharmacological blockade of the OX1 receptors may represent a novel therapeutic approach in the treatment of seizure disorders.

 KEYWORDS:

 6Hz seizures; Maximal electroshock; Orexin A; Orexin receptors; Pentylenetetrazole
BIOSEB Instruments Used
Grip strength test (BIO-GS3)
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Une méthode simple pour quantifier objectivement la force musculaire des rats et souris et l'effet de drogues, toxines, maladies musculaires (ex: myopathie) et neurodégénératives. Cette mesure de force est souvent employée en association avec le test de coordination motrice ROTAROD: un sujet présentant une coordination normale montrera des résultats médiocres en cas de faible force musculaire. Un must pour vos recherches sur l'activité, la coordination et le contrôle musculaire: particulièrement utile pour vos études sur les maladies de Parkinson et Huntington.
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