Dopaminergic response to graded dopamine concentration elicited by four amphetamine doses.
Dopaminergic response to graded dopamine concentration elicited by four amphetamine doses.
复制标题
DOI：
10.1002/syn.20659
复制
发表时间：
2009-09
期刊：
影响因子：
2.3
通讯作者：
Chen, Y. Iris
中科院分区：
文献类型：
--
作者：
Ren, Jiaqian;Xu, Haibo;Choi, Ji-Kyung;Jenkins, Bruce G.;Chen, Y. Iris
我们研究了四种剂量的d -安非他明（AMPH, 0、0.25、0.5、1.0或3.0 mg/kg）对不同多巴胺（DA）浓度的代谢反应。我们比较了DA释放程度（通过微透析）与纹状体cAMP活性和脑血容量（rCBV）变化的全脑图（通过药理学MRI， phMRI）。结果：AMPH增加尾状核/壳核（CPu） DA释放和CPu、伏隔核（NAc）和内侧前额皮质（mPFC） cAMP活性呈线性剂量依赖性（p<0.0001）。cAMP数据表明，高剂量（1 ~ 3mg/kg）时，D1受体诱导的突触后信号转导强于D2受体。phMRI显示，较高剂量的AMPH （3mg/kg （n=7）和1mg/kg (n=6)）可诱导CPu和NAc的rCBV显著增加，但当AMPH为0.5mg/kg （n=6）时，rCBV的增加程度要小得多。相比之下，0.25mg/kg （n=8）的AMPH诱导前内侧CPu和NAc的rCBV显著降低。rCBV对AMPH从低剂量到高剂量的信号转换可能反映了D2/D3刺激与D1/D5刺激平衡的转换。综上所述，突触后信号转导程度与细胞外DA浓度呈线性相关。然而，在低DA浓度范围内，突触前结合可能主导整个DA神经支配。
We studied the metabolic responses to different dopamine (DA) concentrations elicited by four doses of D-amphetamine (AMPH, 0, 0.25, 0.5, 1.0, or 3.0 mg/kg). We compared the degree of DA release (via microdialysis) to striatal cAMP activity and whole brain maps of cerebral blood volume (rCBV) changes (via pharmacological MRI, phMRI). Results: AMPH increased DA release in the caudate/putamen (CPu) and cAMP activity in the CPu, nucleus accumbens (NAc), and medial prefrontal cortex (mPFC) in a linear dose-dependent manner (p<0.0001). The cAMP data suggests that, postsynaptically, signal transduction induced by D1 receptor is stronger than that of D2 receptor at the higher doses (1–3mg/kg). phMRI showed that, while higher doses of AMPH (3mg/kg (n=7) and 1mg/kg (n=6)) induced significant rCBV increases in the CPu and NAc, the degree of rCBV increase was much smaller with AMPH of 0.5mg/kg (n=6). In contrast, AMPH of 0.25mg/kg (n=8) induced significant rCBV decreases in the anteromedial CPu and NAc. The sign switch of rCBV in response to AMPH from low to high doses likely reflects the switching in the balance of D2/D3 stimulation versus D1/D5 stimulation. In conclusion, degree of postsynaptic signal transduction is linearly correlated to the extracellular DA concentration. However, the presynaptic binding may dominate the overall DA innervation at the lower range of DA concentration.
登录
查看更多内容
影响因子：
64.8
作者：
Mulligan, SJ;MacVicar, BA
通讯作者：
MacVicar, BA
影响因子：
4.7
作者：
CAPELLA, P;GHASEMZADEH, MB;WIGHTMAN, RM
通讯作者：
WIGHTMAN, RM
影响因子：
5.3
作者：
Jenkins, BG;Sanchez-Pernaute, R;Isacson, O
通讯作者：
Isacson, O
影响因子：
2.3
作者：
Preece, Mark A.;Sibson, Nicola R.;Sharp, Trevor
通讯作者：
Sharp, Trevor
影响因子：
4.4
作者：
Chen, YCI;Mandeville, JB;Jenkins, BG
通讯作者：
Jenkins, BG