Suarez-Roca H, Lovenberg T, Cubeddu L X
Department of Pharmacology, University of North Carolina, Chapel Hill.
J Pharmacol Exp Ther. 1987 Dec;243(3):840-51.
The olfactory tubercle (OT) is a limbic structure containing high dopamine (DA) and acetylcholine (ACh) concentrations. We performed a comparative study of the DA-ACh interactions, the efficacy of autoreceptor control and the effects of metoclopramide in the OT and the nucleus caudate (striatum). Rabbit brain slices from both regions of the same animal were prelabeled with radioactive DA and/or choline and then superfused. Comparable magnitude of DA and ACh release was evoked by electrical stimulation from both regions. DA release was unaltered, whereas ACh release was inversely related to the stimulation frequency, both in OT and striatum. Apomorphine (APO), a D1-D2 agonist, an LY-171555 (LY), a D2 agonist, inhibited DA and ACh release from OT and striatum with similar EC50 and Emax (maximal percentage of inhibition). However, the maximal degree of inhibition of ACh release achieved with APO, LY or DA in the OT was only one-half that observed in the striatum. In both regions, the inhibitory effects of DA agonists on DA and ACh release were reduced markedly when the number of electrical pulses and/or the frequency of stimulation were increased. l-Sulpiride, a DA D2 antagonist, increased the evoked release of DA and ACh from OT in direct relationship with the frequency of stimulation. In the OT, increases in synaptic DA achieved by administration of amphetamine or by blockade of the neuronal uptake pump with nomifensine inhibited the evoked release of ACh. Again these drug treatments produced only a 40 to 50% inhibition of ACh release. SKF 38393, a D1 agonist, had no effect per se on DA or ACh release in OT slices from control or from reserpine-treated animals (2 mg/kg s.c. for 3 or 7 days). With the exception of one specific dose combination, coadministration of SKF 38393 and LY produced no additive or synergistic effects on DA or ACh release from OT. APO- and LY-induced inhibition of DA and ACh release were antagonized by l-sulpiride. However, 300 nM SCH 23390, a D1 antagonist, reduced APO inhibition of DA and ACh release without affecting the inhibitory action of LY on DA and ACh release. Metoclopramide, "a DA antagonist with poor limbic activity", had a similar affinity for OT (pA2: 7.59) and striatal (pA2: 7.59) DA autoreceptors. Its antidopaminergic efficacy on DA receptors modulating ACh release from OT and striatum was also compared.(ABSTRACT TRUNCATED AT 400 WORDS)
嗅结节（OT）是一个边缘系统结构，含有高浓度的多巴胺（DA）和乙酰胆碱（ACh）。我们对OT和尾状核（纹状体）中DA-ACh的相互作用、自身受体控制的效能以及甲氧氯普胺的作用进行了比较研究。取自同一动物这两个区域的兔脑切片先用放射性DA和/或胆碱进行预标记，然后进行灌流。两个区域的电刺激均能诱发相当程度的DA和ACh释放。在OT和纹状体中，DA释放未发生改变，而ACh释放与刺激频率呈负相关。阿扑吗啡（APO），一种D1-D2激动剂，LY-171555（LY），一种D2激动剂，以相似的半数有效浓度（EC50）和最大效应（Emax，最大抑制百分比）抑制OT和纹状体中DA和ACh的释放。然而，在OT中，APO、LY或DA对ACh释放的最大抑制程度仅为纹状体中观察到的一半。在两个区域中，当电脉冲数量和/或刺激频率增加时，DA激动剂对DA和ACh释放的抑制作用明显减弱。左旋舒必利，一种DA D2拮抗剂，与刺激频率呈正相关地增加OT中诱发的DA和ACh释放。在OT中，通过给予苯丙胺或用诺米芬辛阻断神经元摄取泵所实现的突触DA增加，抑制了诱发的ACh释放。同样，这些药物处理仅产生了40%至50%的ACh释放抑制。SKF 38393，一种D1激动剂，对来自对照动物或经利血平处理的动物（2mg/kg皮下注射，持续3或7天）的OT切片中的DA或ACh释放本身无影响。除了一种特定的剂量组合外，SKF 38393和LY联合给药对OT中DA或ACh释放没有相加或协同作用。APO和LY诱导的DA和ACh释放抑制被左旋舒必利拮抗。然而，300nM SCH 23390，一种D1拮抗剂，降低了APO对DA和ACh释放的抑制作用，而不影响LY对DA和ACh释放的抑制作用。甲氧氯普胺，“一种边缘系统活性较差的DA拮抗剂”，对OT（pA2：7.59）和纹状体（pA2：7.59）的DA自身受体具有相似的亲和力。还比较了其对调节OT和纹状体中ACh释放的DA受体的抗多巴胺能效能。（摘要截断于400字）
