Freo U, Soncrant T T, Ricchieri G L, Wozniak K M, Larson D M, Rapoport S I
Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892.
Brain Res. 1990 Mar 19;511(2):209-16. doi: 10.1016/0006-8993(90)90163-6.
The time course and relation to dose of regional cerebral metabolic rates for glucose (rCMRglc) and of motor behavior were measured in awake male adult Fischer-344 rats after administration of meta-chlorophenylpiperazine (MCPP), a serotonin-1B receptor agonist. rCMRglc was determined, using the quantitative autoradiographic [14C]deoxyglucose technique, in 71 brain regions at 5, 15, 30 and 60 min after administration of MCPP 2.5 mg/kg i.p., and at 15 min after MCPP 25 and 40 mg/kg. The time course of performance on a rotating rod was measured periodically for 60 min after MCPP 2.5 mg/kg, a dose which impaired locomotion and reduced rCMRglc maximally at 15-30 min after its administration. At 15 min, rCMRglc declined significantly in 28 (40%) of the areas studied (mean decline 16%). Most regions affected were telencephalic or diencephalic, corresponding to the projection areas of serotonergic fibers arising from the raphe nuclei. After higher doses of MCPP, a behavioral serotonin syndrome was observed with both rCMRglc increases and decreases (25 mg/kg) or only rCMRglc increases (40 mg/kg). Whereas behavioral and metabolic activation induced by high doses of MCPP may result from stimulation at postsynaptic serotonin receptors, rCMRglc reductions and hypomotility produced by MCPP 2.5 mg/kg resemble the effects of serotonin receptor antagonists and suggest that, at this low dose, MCPP acts at modulatory serotonin autoreceptors to reduce endogenous serotonin release.
在成年雄性清醒Fischer-344大鼠腹腔注射5-羟色胺-1B受体激动剂间氯苯哌嗪（MCPP）后，测定其葡萄糖区域脑代谢率（rCMRglc）的时程及其与剂量的关系，以及运动行为。采用定量放射自显影[14C]脱氧葡萄糖技术，在腹腔注射2.5mg/kg MCPP后5、15、30和60分钟，以及25mg/kg和40mg/kg MCPP后15分钟，测定71个脑区的rCMRglc。在注射2.5mg/kg MCPP后，每隔一段时间测量旋转杆上的行为表现时程60分钟，该剂量会损害运动能力，并在给药后15 - 30分钟使rCMRglc最大程度降低。在15分钟时，所研究的28个（40%）区域的rCMRglc显著下降（平均下降16%）。受影响的大多数区域是端脑或间脑，对应于中缝核产生的5-羟色胺能纤维的投射区域。给予更高剂量的MCPP后，观察到行为性5-羟色胺综合征，rCMRglc既有增加也有减少（25mg/kg），或者只有rCMRglc增加（40mg/kg）。高剂量MCPP诱导的行为和代谢激活可能是由于突触后5-羟色胺受体的刺激，而2.5mg/kg MCPP产生的rCMRglc降低和运动减弱类似于5-羟色胺受体拮抗剂的作用，表明在这个低剂量下，MCPP作用于调节性5-羟色胺自身受体以减少内源性5-羟色胺释放。
