Mosko S S, Jacobs B L
Brain Res. 1977 Jan 7;119(2):291-303. doi: 10.1016/0006-8993(77)90312-2.
The hypothesis that the activity of serotonin (5-HT)-containing neurons of the midbrain raphe is subject to negative neuronal feedback regulation was examined. This hypothesis is based primarily on the observation that the administration of drugs which increase the synaptic availability of 5-HT depress midbrain raphe neuron discharge. Since the preponderance of midbrain raphe efferents are ascending, transections which interrupt both the main efferent outflow, as well as all inputs from anterior levels, ought to disrupt the functional integrity of a neuronal feedback loop. The effect of complete transections of the neuraxis placed just rostral to the midbrain raphe nuclei on the efficacy of two drugs which elevate synaptic serotonin, chlorimipramine and p-chloroamphetamine, was investigated in the chloral hydrate anesthetized rat. Such transections neither blocked nor attenuated the depressive effect of intravenously administered chlorimipramine (0.33 or 0.15 mg/kg) or p-chloroamphetamine (1.25 mg/kg) on midbrain raphe unit discharge. These results suggest that neuronal feedback involving the forebrain dose not mediate the depressive effect of drugs which elevate synaptic serotonin on midbrain raphe neuronal activity. An action at serotonergic synapses intrinsic to the midbrain raphe is suggested as an explanation for the persistence of drug effects in transected animals.
对中脑缝际含5-羟色胺（5-HT）神经元的活动受负性神经元反馈调节这一假说进行了研究。该假说主要基于以下观察结果：给予能增加5-HT突触可利用性的药物会抑制中脑缝际神经元放电。由于中脑缝际传出纤维大多是上行的，中断主要传出纤维以及来自前部水平的所有输入的横断应该会破坏神经元反馈回路的功能完整性。在水合氯醛麻醉的大鼠中，研究了恰好在中脑缝际核前方进行的全脑横断对两种能提高突触5-羟色胺水平的药物——氯米帕明和对氯苯丙胺——作用效果的影响。这种横断既未阻断也未减弱静脉注射氯米帕明（0.33或0.15毫克/千克）或对氯苯丙胺（1.25毫克/千克）对中脑缝际单位放电的抑制作用。这些结果表明，涉及前脑的神经元反馈并不介导能提高突触5-羟色胺水平的药物对中脑缝际神经元活动的抑制作用。有人提出，中脑缝际固有的5-羟色胺能突触处的作用可以解释横断动物中药物作用的持续存在。
