کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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319895 | 539613 | 2008 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Attenuation of methamphetamine-induced effects through the antagonism of sigma (σ) receptors: Evidence from in vivo and in vitro studies Attenuation of methamphetamine-induced effects through the antagonism of sigma (σ) receptors: Evidence from in vivo and in vitro studies](/preview/png/319895.png)
Methamphetamine (METH) and many other abused substances interact with σ receptors. σ receptors are found on dopaminergic neurons and can modulate dopaminergic neurotransmission. Antisense knock down of σ receptors also mitigates METH-induced stimulant effects, suggesting that these proteins are viable medication development targets for treating psychostimulant abuse. In the present study, AC927, a σ receptor antagonist, was evaluated for its ability to attenuate METH-induced effects in vivo and in vitro. Radioligand binding studies showed that AC927 had preferential affinity for σ receptors compared to 29 other receptors, transporters and ion channels. Pretreatment of male, Swiss Webster mice with AC927 significantly attenuated METH-induced locomotor stimulation, striatal dopamine depletions, striatal dopamine transporter reductions, and hyperthermia. When the neurotoxicity of METH was further examined in vitro under temperature-controlled conditions, co-incubation with AC927 mitigated METH-induced cytotoxicity. Together, the results demonstrate that AC927 protects against METH-induced effects, and suggests a new strategy for treating psychostimulant abuse.
Journal: European Neuropsychopharmacology - Volume 18, Issue 12, December 2008, Pages 871–881