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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