腹侧被盖区的6-羟基多巴胺损伤会阻断吗啡诱导的自我刺激增强，但不会阻断苯丙胺诱导的自我刺激增强。

6-OHDA lesions of the ventral tegmental area block morphine-induced but not amphetamine-induced facilitation of self-stimulation.

作者信息

Hand T H, Franklin K B

出版信息

Brain Res. 1985 Mar 4;328(2):233-41. doi: 10.1016/0006-8993(85)91034-0.

Abstract

The biphasic effect of morphine on intracranial self-stimulation (ICSS) (suppression followed by facilitation) was examined in rats following injections of 6-OHDA or vehicle into the ventral tegmental area (VTA). During 7 days of chronic administration of morphine, sham-lesioned animals gradually developed tolerance to the rate-reducing effects of the drug and a concurrent sensitization to its rate-enhancing effects (measured 1 and 3 h post-injection, respectively). VTA lesioned rats showed neither tolerance to the rate suppression nor any facilitation of ICSS throughout testing. Amphetamine's facilitation of ICSS remained intact in all subjects. The lesion was restricted to the VTA cell bodies but produced a significant depletion of dopamine (DA) in both the nucleus accumbens and in the striatum. Morphine facilitation of ICSS is suggested to be dependent on an indirect opiate receptor-VTA DA cell interaction. It is also proposed that amphetamine facilitation of ICSS is a 'mass action' effect involving the full DA terminal area of the forebrain rather than a subregion of that area.

摘要

在大鼠腹侧被盖区（VTA）注射6-羟基多巴胺（6-OHDA）或赋形剂后，研究了吗啡对颅内自我刺激（ICSS）的双相效应（先抑制后促进）。在吗啡慢性给药的7天期间，假损伤动物逐渐对药物的降低速率效应产生耐受性，并同时对其提高速率效应产生敏化（分别在注射后1小时和3小时测量）。在整个测试过程中，VTA损伤的大鼠既未表现出对速率抑制的耐受性，也未表现出ICSS的任何促进作用。苯丙胺对ICSS的促进作用在所有受试者中均保持不变。损伤仅限于VTA细胞体，但导致伏隔核和纹状体中的多巴胺（DA）显著耗竭。吗啡对ICSS的促进作用被认为依赖于间接的阿片受体-VTA DA细胞相互作用。还提出苯丙胺对ICSS的促进作用是一种“整体作用”效应，涉及前脑的整个DA终末区，而不是该区域的一个子区域。