Benfenati F, Ferretti C, Cimino M, Vantini G, Lipartiti M, Muccioli G, Di Carlo R, Algeri S
Pharmacol Res Commun. 1986 May;18(5):431-49. doi: 10.1016/0031-6989(86)90164-5.
Chronic treatment with Domperidone (DOM) had no effect on basal prolactin (PRL) secretion or basal levels of Dopamine (DA) metabolites in basal hypothalamus and striatum as compared with the vehicle treated rats. Animals chronically treated with DOM did not present tolerance to a challenge dose of Haloperidol (HAL) and DOM either measuring PRL secretion or striatal DA metabolite levels. The PRL-induced increase in hypothalamic 3,4-dihydroxyphenylacetic acid (DOPAC) was reduced. These results were accompanied by no change at striatal DA receptors, a slight reduction in density-affinity at hypothalamic DA receptors but clear-cut modification in pituitary DA receptors with the appearance of a high affinity-low capacity binding sites. It can be surmised that sustained hyperprolactinemia may induce tolerance in hypothalamic Tuberoinfundibular (TIDA) neurons involved in the inhibitory control of PRL secretion and a change in the kinetic properties of pituitary DA receptors, but it does not consistently affect the activity of the nigro-striatal DA system.
与赋形剂处理的大鼠相比，多潘立酮（DOM）长期治疗对基础催乳素（PRL）分泌或下丘脑基部和纹状体中多巴胺（DA）代谢物的基础水平没有影响。长期用DOM治疗的动物，无论是测量PRL分泌还是纹状体DA代谢物水平，对氟哌啶醇（HAL）和DOM的激发剂量均未表现出耐受性。PRL诱导的下丘脑3,4-二羟基苯乙酸（DOPAC）增加有所减少。这些结果伴随着纹状体DA受体无变化，下丘脑DA受体的密度亲和力略有降低，但垂体DA受体有明显改变，出现了高亲和力-低容量结合位点。可以推测，持续性高催乳素血症可能会诱导参与PRL分泌抑制控制的下丘脑结节漏斗部（TIDA）神经元产生耐受性，并改变垂体DA受体的动力学特性，但并不一致地影响黑质-纹状体DA系统的活性。
