Kalivas P W, Richardson-Carlson R
Am J Physiol. 1986 Aug;251(2 Pt 2):R243-9. doi: 10.1152/ajpregu.1986.251.2.R243.
Many lines of evidence support the possibility that the opioid pentapeptides Met- and Leu-enkephalin can modulate dopamine neurons in the ventral tegmental area (VTA). Thus microinjection of enkephalin analogues into the VTA of rats produces a dopamine-dependent increase in spontaneous motor activity and an increase in dopamine metabolism in certain mesolimbic dopamine terminal fields, such as the nucleus accumbens. To determine if these effects can be produced by endogenous enkephalins, an enkephalinase A inhibitor, thiorphan, was microinjected into the VTA to inhibit enkephalin metabolism. Thiorphan produced a dose-dependent (0.3-3.33 micrograms) increase in spontaneous motor activity that was blocked by pretreatment with the opioid antagonist naloxone (2.0 mg/kg ip) or the dopamine antagonist haloperidol (0.1 mg/kg ip). Thiorphan injection into the VTA increased dopamine metabolism in the nucleus accumbens, prefrontal cortex, and septum but not in the striatum. In all brain regions the increase in dopamine metabolism was blocked by pretreatment with naloxone. These data demonstrate that endogenous enkephalin in the VTA can increase the activity of A10 dopamine neurons, supporting a physiological role for enkephalin in mesolimbic and mesocortical dopamine-mediated behaviors.
许多证据支持阿片类五肽甲硫氨酸脑啡肽和亮氨酸脑啡肽可能调节腹侧被盖区（VTA）多巴胺能神经元的可能性。因此，将脑啡肽类似物微量注射到大鼠的VTA中，会导致自发运动活动出现多巴胺依赖性增加，并且在某些中脑边缘多巴胺终末场（如伏隔核）中多巴胺代谢增加。为了确定内源性脑啡肽是否能产生这些效应，将脑啡肽酶A抑制剂硫喷妥微量注射到VTA中以抑制脑啡肽代谢。硫喷妥使自发运动活动呈剂量依赖性（0.3 - 3.33微克）增加，这种增加被阿片拮抗剂纳洛酮（2.0毫克/千克腹腔注射）或多巴胺拮抗剂氟哌啶醇（0.1毫克/千克腹腔注射）预处理所阻断。向VTA注射硫喷妥可增加伏隔核、前额叶皮质和隔区的多巴胺代谢，但不会增加纹状体的多巴胺代谢。在所有脑区，多巴胺代谢的增加都被纳洛酮预处理所阻断。这些数据表明，VTA中的内源性脑啡肽可增加A10多巴胺能神经元的活性，支持脑啡肽在中脑边缘和中脑皮质多巴胺介导行为中的生理作用。
