CM156, a high affinity sigma ligand, attenuates the stimulant and neurotoxic effects of methamphetamine in mice

NEUROPHARMACOLOGY

卷:61

Article

Kaushal, Nidhi¹  Seminerio, Michael J.¹  Shaikh, Jamaluddin^1,2,3  Medina, Mark A.¹  Mesangeau, Christophe^2,3  Wilson, Lisa L.^2,3  McCurdy, Christopher R.^2,3  Matsumoto, Rae R.^1,2,3 

[1] W Virginia Univ, Sch Pharm, Dept Basic Pharmaceut Sci, Morgantown, WV 26506 USA

[2] Univ Mississippi, Sch Pharm, Dept Pharmacol, University, MS 38677 USA

[3] Univ Mississippi, Sch Pharm, Dept Med Chem, University, MS 38677 USA

关键词: Dopamine;    Methamphetamine;    Serotonin;    sigma Receptors;    Locomotor;    Neurotoxicity;   

DOI  :  10.1016/j.neuropharm.2011.06.028

来源: Elsevier

【 摘 要 】

Methamphetamine (METH) is a highly addictive psychostimulant drug of abuse. Low and high dose administration of METH leads to locomotor stimulation, and dopaminergic and serotonergic neurotoxicity, respectively. The behavioral stimulant and neurotoxic effects of METH can contribute to addiction and other neuropsychiatric disorders, thus necessitating the identification of potential pharmacotherapeutics against these effects produced by METH. METH binds to sigma receptors at physiologically relevant concentrations. Also, sigma receptors are present on and can modulate dopaminergic and serotonergic neurons. Therefore, sigma receptors provide a viable target for the development of pharmacotherapeutics against the adverse effects of METH. In the present study, CM156, a sigma receptor ligand with high affinity and selectivity for sigma receptors over 80 other non-sigma binding sites, was evaluated against METH-induced stimulant, hyperthermic, and neurotoxic effects. Pretreatment of male, Swiss Webster mice with CM 156 dose dependently attenuated the locomotor stimulation, hyperthermia, striatal dopamine and serotonin depletions, and striatal dopamine and serotonin transporter reductions produced by METH, without significant effects of CM156 on its own. These results demonstrate the ability of a highly selective sigma ligand to mitigate the effects of METH. (C) 2011 Elsevier Ltd. All rights reserved.

【 授权许可】

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