Nucleus accumbens AGS3 expression drives ethanol seeking through Gβγ
Nucleus accumbens AGS3 expression drives ethanol seeking through Gβγ
复制标题
DOI：
10.1073/pnas.0706999105
复制
发表时间：
2008-08-26
影响因子：
11.1
通讯作者：
Diamond, Ivan
中科院分区：
文献类型：
--
作者：
Bowers, M. Scott;Hopf, F. Woodward;Diamond, Ivan
大约90%的酗酒者在4年内复发，部分原因是寻求酒精（乙醇）的动机增强。一种新的G蛋白调节剂（Gpsm 1/AGS 3）在大鼠延髓核核心（NAcore），但不是在其他边缘核在禁欲从操作性乙醇自我管理上调。此外，NAcore AGS 3敲低在强迫性人类EtOH寻求的新型大鼠模型中将EtOH寻求降低至戒断前水平。AGS 3可以抑制G蛋白Gi α介导的信号传导并刺激G β γ介导的信号传导。因此，G β γ的螯合而不是Gi α敲低显著降低了寻求禁欲前水平的EtOH。因此，AGS 3和G β γ被假设为控制禁欲期间寻求EtOH的不受控制的动机。戒断期间AGS 3上调可能是复发期间从社会消费向强迫性寻求过渡的关键决定因素。
Approximately 90% of alcoholics relapse within 4 years, in part because of an enhanced motivation to seek alcohol (EtOH). A novel G protein modulator (Gpsm1/AGS3) was up-regulated in the rat nucleus accumbens core (NAcore) but not in other limbic nuclei during abstinence from operant EtOH self-administration. Furthermore, NAcore AGS3 knockdown reduced EtOH seeking to pre-abstinence levels in a novel rat model of compulsive, human EtOH seeking. AGS3 can both inhibit G protein Gi alpha-mediated signaling and stimulate G beta gamma-mediated signaling. Accordingly, sequestration of G beta gamma, but not Gi alpha knockdown, significantly reduced EtOH seeking to pre-abstinence levels. Thus, AGS3 and G beta gamma are hypothesized to gate the uncontrolled motivation to seek EtOH during abstinence. AGS3 up-regulation during abstinence may be a key determinant of the transition from social consumption to compulsion-like seeking during relapse.