Expression of c-fos mRNA in the basal ganglia associated with contingent tolerance to amphetamine-induced hypophagia.
Expression of c-fos mRNA in the basal ganglia associated with contingent tolerance to amphetamine-induced hypophagia.
复制标题
基底神经节中 c-fos mRNA 的表达与对安非他明诱导的吞咽不足的偶然耐受性相关。
DOI：
10.1016/j.bbr.2008.11.026
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发表时间：
2009
影响因子：
2.7
通讯作者：
Wolgin,DavidL
中科院分区：
文献类型：
--
作者：
Bachand,KimberleeD;Guthrie,KathleenM;Wolgin,DavidL
对精神兴奋剂的摄食减少作用的耐受性取决于在中毒时能够获得食物。长期注射这种药物的老鼠在获得食物的情况下学会了抑制刻板的运动，这会干扰进食。与此相反，对照组在获得食物后给予药物，不会学会抑制刻板行为，因此不会变得耐受。为了确定基底神经节在这种现象中的作用，我们使用原位杂交来测量c-fos mRNA的表达，这是一种神经激活的标志物，在耐受和非耐受大鼠的大脑中。在进食前长期注射安非他明的老鼠学会了抑制刻板的动作，而在进食后给予药物的对照组则没有。急性注射安非他明后，这两个组有较高水平的c-fos mRNA比盐水处理的对照组在整个纹状体，在神经核的核心，腹侧苍白球和层V-VI的运动皮层。相比之下，耐受大鼠，这已经学会了抑制刻板，有较高水平的c-fos mRNA比安非他明和盐水处理的控制在脚内核，苍白球，丘脑底核，脚桥核，核壳，嗅结节，体感皮层，和第二-IV层的运动皮层。这些数据表明，安非他明诱导的刻板印象的学习抑制涉及激活背侧纹状体通路先前牵连在响应选择以及腹侧纹状体，长期牵连在食欲的动机和强化。
Tolerance to the hypophagic effect of psychostimulants is contingent on having access to food while intoxicated. Rats given chronic injections of such drugs with access to food learn to suppress stereotyped movements, which interfere with feeding. In contrast, controls given the drug after food access do not learn to suppress stereotypy and, therefore, do not become tolerant. To determine the role of the basal ganglia in this phenomenon, we used in situ hybridization to measure the expression of c-fos mRNA, a marker for neural activation, in the brains of tolerant and nontolerant rats. Rats given chronic amphetamine injections prior to food access learned to suppress stereotyped movements, whereas yoked controls given the drug after feeding did not. Following an acute injection of amphetamine, both of these groups had higher levels of c-fos mRNA than saline-treated controls throughout the striatum, in the nucleus accumbens core, the ventral pallidum and layers V–VI of the motor cortex. In contrast, tolerant rats, which had learned to suppress stereotypy, had higher levels of c-fos mRNA than both amphetamine- and saline-treated controls in the entopeduncular nucleus, globus pallidus, subthalamic nucleus, pedunculopontine nucleus, nucleus accumbens shell, olfactory tubercle, somatosensory cortex, and layers II–IV of motor cortex. These data suggest that the learned suppression of amphetamine-induced stereotypy involves the activation of dorsal striatal pathways previously implicated in response selection as well as the ventral striatum, long implicated in appetitive motivation and reinforcement.