Ren Jiaqian, Xu Haibo, Choi Ji-Kyung, Jenkins Bruce G, Chen Y Iris
Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, USA.
Synapse. 2009 Sep;63(9):764-72. doi: 10.1002/syn.20659.
We studied the metabolic responses to different 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) with striatal cAMP activity and whole brain maps of cerebral blood volume (rCBV) changes (via pharmacological MRI, phMRI).
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 suggest that, postsynaptically, signal transduction induced by D1 receptor is stronger than that of D2 receptor at the higher doses (1-3 mg/kg). phMRI showed that, while higher doses of AMPH (3 mg/kg (n = 7) and 1 mg/kg (n = 6)) induced significant rCBV increases in the CPu and NAc, the degree of rCBV increase was much smaller with AMPH of 0.5 mg/kg (n = 6). In contrast, AMPH of 0.25 mg/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 vs. 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.
我们研究了四剂右旋苯丙胺（AMPH，0、0.25、0.5、1.0或3.0mg/kg）引发的对不同多巴胺（DA）浓度的代谢反应。我们通过微透析比较了纹状体中环磷酸腺苷（cAMP）活性和全脑脑血容量（rCBV）变化图谱（通过药理磁共振成像，phMRI）来评估DA释放程度。
AMPH以线性剂量依赖性方式增加尾状核/壳核（CPu）中的DA释放以及CPu、伏隔核（NAc）和内侧前额叶皮质（mPFC）中的cAMP活性（P<0.0001）。cAMP数据表明，在较高剂量（1 - 3mg/kg）时，突触后由D1受体诱导的信号转导强于D2受体。phMRI显示，虽然较高剂量的AMPH（3mg/kg（n = 7）和1mg/kg（n = 6））在CPu和NAc中诱导了显著的rCBV增加，但0.5mg/kg的AMPH（n = 6）时rCBV增加程度要小得多。相反，0.25mg/kg的AMPH（n = 8）在前内侧CPu和NAc中诱导了显著的rCBV降低。rCBV对AMPH从低剂量到高剂量反应的正负转换可能反映了D2/D3刺激与D1/D5刺激平衡的转换。总之，突触后信号转导程度与细胞外DA浓度呈线性相关。然而，在较低DA浓度范围内，突触前结合可能主导整体DA神经支配。
