Chen Y Iris, Choi Ji-Kyung, Jenkins Bruce G
MGH-NMR Center and Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Synapse. 2005 Feb;55(2):80-8. doi: 10.1002/syn.20091.
Adenosine receptors in the basal ganglia are implicated in regulation of dopamine function and release. We investigated the interactions between dopamine receptors and adenosine receptors in the basal ganglia using pharmacologic MRI (phMRI) in rats. Stimulation of dopamine receptors was achieved using administration of 2 mg/kg of amphetamine. Then we investigated the antagonism of these changes using the selective A2a receptor antagonist 3,7-dimethyl-1-propargylaxanthine (DMPX). Amphetamine alone caused large increases (10-30%) in relative cerebral blood volume (rCBV) in caudate/putamen (CPu), nucleus accumbens (NAcc), thalamus, and frontal and cingulate cortices with changes that persisted for 70-80 min. DMPX alone (5 mg/kg) induced decreases in rCBV (approximately 8-10%) in NAcc, CPu, and olfactory tubercule, with smaller changes in thalamus (-6%) consistent with the regional distribution of A2a receptors. We examined the interactions between amphetamine and DMPX by assessing the effects of DMPX (5 mg/kg) administration 20 min after injection of 3 mg/kg amphetamine. These experiments showed that DMPX immediately decreased the rCBV increase induced by amphetamine in NAcc, CPu, and thalamus but not in cingulate or sensorimotor cortex. Companion microdialysis experiments showed that dopamine release in CPu was decreased in a similar manner. These experiments demonstrate the utility of phMRI for probing, in a noninvasive manner, the temporal and spatial dynamics of neurotransmitter interactions.
基底神经节中的腺苷受体与多巴胺功能及释放的调节有关。我们在大鼠中使用药物磁共振成像（phMRI）研究了基底神经节中多巴胺受体与腺苷受体之间的相互作用。通过给予2mg/kg的苯丙胺来刺激多巴胺受体。然后我们使用选择性A2a受体拮抗剂3,7-二甲基-1-丙炔基黄嘌呤（DMPX）研究这些变化的拮抗作用。单独使用苯丙胺会导致尾状核/壳核（CPu）、伏隔核（NAcc）、丘脑以及额叶和扣带回皮质的相对脑血容量（rCBV）大幅增加（10 - 30%），且这些变化持续70 - 80分钟。单独使用DMPX（5mg/kg）会导致NAcc、CPu和嗅结节的rCBV降低（约8 - 10%），丘脑中的变化较小（-6%），这与A2a受体的区域分布一致。我们通过评估在注射3mg/kg苯丙胺20分钟后给予DMPX（5mg/kg）的效果，来研究苯丙胺与DMPX之间的相互作用。这些实验表明，DMPX能立即降低苯丙胺在NAcc、CPu和丘脑中诱导的rCBV增加，但在扣带回或感觉运动皮层中则不然。配套的微透析实验表明，CPu中的多巴胺释放也以类似方式减少。这些实验证明了phMRI在以非侵入性方式探究神经递质相互作用的时空动态方面的实用性。
