کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6276710 | 1614900 | 2011 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Cognitive, Behavioral, and Systems NeuroscienceResearch PaperGabapentin blocks methamphetamine-induced sensitization and conditioned place preference via inhibition of α2/δ-1 subunits of the voltage-gated calcium channels Cognitive, Behavioral, and Systems NeuroscienceResearch PaperGabapentin blocks methamphetamine-induced sensitization and conditioned place preference via inhibition of α2/δ-1 subunits of the voltage-gated calcium channels](/preview/png/6276710.png)
Our previous investigation demonstrated that repeated administration of morphine significantly enhanced α2/δ-1 subunit expression in the frontal cortex and limbic forebrain of mice as well as morphine-induced place preference. However, little is known about regulatory mechanisms of α2/δ-1 subunit expression in conditioned place preference by methamphetamine (METH). In the present study, we investigated the role of α2/δ-1 subunit of voltage-gated calcium channels (VGCCs) in the mouse brain under repeated treatment with METH. The level of α2/δ-1 subunit increased significantly in the limbic forebrain including the nucleus accumbens and the frontal cortex of mice showing METH-induced sensitization. Under these conditions, the development of behavioral sensitization induced by the intermittent administration of METH was significantly suppressed by the co-administration of gabapentin (GBP) with binding activity to an exofacial epitope of α2/δ-1 subunit. Furthermore, GBP administered i.c.v. caused a dose-dependent inhibition of the METH-induced place preference. Chronic GBP treatment at the dose alleviating sensitization and place preference significantly reduced the elevation of α2/δ-1 subunit of VGCC induced by the repeated administration of METH in the limbic forebrain and frontal cortex, whereas there were no changes in the increase of α2/δ-1 subunit mRNA. These findings indicate that α2/δ-1 subunit plays a critical role in the development of METH-induced place preference following neuronal plasticity, and that GBP, which significantly suppressed METH-induced place preference by its possible inhibitory action of α2/δ subunit to neuronal membrane, may possibly be used as an alternative drug to treat or prevent drug dependence.
Research highlightsâ¶The level of α2/δ-1 subunit increased in the limbic forebrain and frontal cortex showing METH-induced sensitization. â¶The development of behavioral sensitization induced by METH was suppressed by co-administration of gabapentin. â¶Gabapentin inhibited METH-induced place preference. â¶Gabapentin may reduce trafficking of α2/δ-1 subunit proteins to plasma membrane.
Journal: Neuroscience - Volume 176, 10 March 2011, Pages 328-335