Wyniki wyszukiwania - Biblioteka Nauki

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The role of FAAH and MAGL inhibitors in anxiety disorders

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Burat M. , Gibula-Tarlowska E. , Skiba W. , Orzelska-Gorka J. , Kedzierska E.

World Scientific News

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2020

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tom 139

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nr 2

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Nitric oxide synthase inhibitors protect against the development of sensitization to mephedrone in mice

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Talarek S. , Listos J. , Orzelska-Gorka J. , Bielecka G. , Kotlińska J.

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nr Suppl.1

EN

INTRODUCTION: Mephedrone is a cathinone derivative that possesses powerful psychostimulant and hallucinogenic effects. It is known that mephedrone may act by increasing release and reuptake inhibition of serotonine and dopamine. Mephedrone has a high abuse and health risk liability, with increased tolerance, sensitization, impaired control and a compulsion to use, the predominant reported dependence symptoms. However, the precise mechanisms underlying its psychoactive effects remain unclear. NO is produced from L-arginine by a reaction catalyzed by NO synthase in response to activation of excitatory amino acid receptors. It acts as an endogenous activator of guanylate cyclase and thereby increases the level of an intracellular second messenger, cGMP. NO, a novel neuronal messenger, is involved in a number of physiological and pathophysiological processes. Recent studies indicate that NO may play a role in tolerance, dependence and sensitization to the addictive drugs such as opioids, ethanol, psychostimulants and nicotine. AIM(S): The present studies were undertaken to determine the influence of NO synthase inhibitors: NG‑nitro-L-arginine methyl ester (L-NAME), non-selective NO synthase inhibitor and 7-nitroindazole, selective inhibitor of neuronal NO synthase, in the development of sensitization to locomotor activity following repeated mephedrone administration in mice. METHOD(S): Sensitization to locomotor activity was induced by chronic administration of mephedrone (2.5 mg/kg/day ip, 5 days) in male albino Swiss mice. L-NAME (25, 50 mg/kg) and 7-nitroindazole (10, 20 mg/kg) were injected ip for 5 days, 20 min before mephedrone administration. After a 7-day interval, acute dose of mehedrone (2.5 mg/kg) was injected and locomotor activity was assessed for 30 min. RESULTS: The present experiments demonstrated that coadministration of NO synthase inhibitors: L-NAME and 7-nitroindazole with mephedrone for 5 days protect against the development of mephedrone-induced sensitization to locomotor activity in mice. CONCLUSIONS: The results of the present study suggest that NO may play a role in the development of sensitization to mephedrone in mice. FINANCIAL SUPPORT: The reported study was supported by Founds for Statutory Activity of Medical University of Lublin, Poland.

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Hyperoside isolated from Impatiens glandulifera Royle alleviates depressive and anxiety-like responses in a mouse model of posttraumatic stress disorder

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Orzelska-Gorka J. , Szewczyk K. , Kedzierska E. , Glowacka E. , Kruk-Slomka M. , Biala G.

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nr Suppl.1

EN

INTRODUCTION: Posttraumatic stress disorder (PTSD) is a chronic and prevalent psychiatric condition that may develop following exposure to traumatic events. Depressive symptoms and anxiety belong to the most frequent symptoms observed in PTSD patients. Less than 30% of PTSD patients achieve full remission with the use of available drugs. For this purpose, there is a clear need to develop more efficient and safer drugs as alternative and/or complimentary therapy for PTSD. Hyperoside (HYP) is one of the polyphenols found in Impatiens glandulifera. Our previous experiments showed that HYP exerted antidepressant effects, both after acute and chronic (14 days) treatment in mice in the forced swimming test (FST; data not published). AIM(S): The present study aimed to investigate the effect of HYP on the behavioural impairments (depression and anxiety) induced by a mouse single prolonged stress (mSPS) – a rodent model of PTSD. METHOD(S): mSPS protocol: mice were exposed to a series of short stressors. In particular, they were restrained for 2 h in a Plexiglas tubes (50 ml), placed in glass beakers and immersed in water (23‑25°C) for a group swim (10 min). Then, they were exposed to a beaker of soiled bedding taken from cages of rats (15 min), and at the end, they were exposed to anhydrous diethyl ether until they lost consciousness (approx. 2 – 3 min). Seven days after exposure to SPS, the administration of substances was started (during next 14 days). Then, animals were subjected to behavioural tests, including the elevated plus-maze test (EPM), measurement of locomotion, and FST. RESULTS: Mice given chronically HYP (3.75 and 7.5 mg/kg) after exposure to mSPS exhibited a reduction of immobility time in FST, and more open arm entries and longer open arms duration in EPM without affecting locomotor activity as compared to control‑mSPS group. CONCLUSIONS: In summary, our results suggested the potential of HYP in alleviating the mSPS-induced depressive and anxiety‑like responses.