Evidence of increased dopamine receptor signaling in food-restricted rats
Evidence of increased dopamine receptor signaling in food-restricted rats
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DOI：
10.1016/s0306-4522(03)00227-6
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发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Yamamoto, N
中科院分区：
文献类型：
--
作者：
Carr, KD;Tsimberg, Y;Yamamoto, N
众所周知，长期的食物限制增强了对滥用药物的奖励和运动激活作用的敏感性。然而，这些行为效应背后的神经适应性尚未得到表征。本研究的目的是探讨食物限制产生增加多巴胺（DA）受体功能的可能性，这在行为，信号转导和立即早期基因表达中是显而易见的。在前两个实验中，大鼠接受脑室内（i. c. v.）注射D1 DA受体激动剂SKF-82958和D2/3 DA受体激动剂喹吡罗。这两种激动剂在食物限制的大鼠中产生的运动激活作用比自由进食的大鼠更大。此外，SKF-82958在尾壳核（CPu）和延髓核（Nac）中诱导的Fos免疫染色在食物限制的大鼠中比自由进食的大鼠更大，在苍白球和腹侧苍白球中诱导的染色也是如此。在接下来的两个实验中，将由CPu和Nac制备的神经元膜暴露于SKF-82958和喹吡罗。尽管有记录表明D1 DA受体介导的c-fos诱导中涉及环AMP（cAMP）信号传导，但SKF-82958对CPu和Nac中腺苷酸环化酶（AC）活性的刺激在组间无差异。然而，食物限制，减少AC刺激的直接酶刺激剂，毛喉素，但不氟化钠或氯化锰，表明AC表达的转变，催化效率较低的亚型。最后，食物限制增加了喹吡罗刺激的CPu中[S-35]三磷酸鸟苷-γ S结合，表明D2 DA受体和G（i）之间的功能偶联增加可能是喹吡罗增强的行为和苍白球c-Fos反应的原因。本研究的结果支持这一假设，即食物限制导致神经适应的水平上的突触后D1和D2受体轴承细胞，反过来，介导增强的行为和转录反应DA。这些增强的反应的信号通路介导的仍然是完全阐明。(C)2003年IBRO。由爱思唯尔科技有限公司出版。保留所有权利。
it is well established that chronic food restriction enhances sensitivity to the rewarding and motor-activating effects of abused drugs. However, neuroadaptations underlying these behavioral effects have not been characterized. The purpose of the present study was to explore the possibility that food restriction produces increased dopamine (DA) receptor function that is evident in behavior, signal transduction, and immediate early gene expression. In the first two experiments, rats received intracerebroventricular (i.c.v.) injections of the D1 DA receptor agonist SKF-82958, and the D2/3 DA receptor agonist quinpirole. Both agonists produced greater motor-activating effects in food-restricted than ad libitum-fed rats. In addition, Fos-immunostaining induced by SKF-82958 in caudate-putamen (CPu) and nucleus accumbens (Nac) was greater in food-restricted than ad libitum-fed rats, as was staining induced by quinpirole in globus pallidus and ventral pallidum. In the next two experiments, neuronal membranes prepared from CPu and Nac were exposed to SKF-82958 and quinpirole. Despite the documented involvement of cyclic AMP (cAMP) signaling in D1 DA receptor-mediated c-fos induction, stimulation of adenylyl cyclase (AC) activity by SKF-82958 in CPu and Nac did not differ between groups. Food restriction did, however, decrease AC stimulation by the direct enzyme stimulant, forskolin, but not NaF or MnCl2, suggesting a shift in AC expression to a less catalytically efficient isoform. Finally, food restriction increased quinpirole-stimulated [S-35]guanosine triphosphate-gammaS binding in CPu, suggesting that increased functional coupling between D2 DA receptors and G(i) may account for the augmented behavioral and pallidal c-Fos responses to quinpirole. Results of this study support the hypothesis that food restriction leads to neuroadaptations at the level of postsynaptic D1 and D2 receptor-bearing cells which, in turn, mediate augmented behavioral and transcriptional responses to DA. The signaling pathways mediating these augmented responses remain to be fully elucidated. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.