Heidbreder C, Roques B, Vanderhaeghen J J, De Witte P
University of Louvain, Lab. Psychobiologie, B-1348 Louvain-La-Neuve, Belgium.
Neurochem Int. 1988;12(3):347-50. doi: 10.1016/0197-0186(88)90173-8.
The ventral tegmental area contains a high density of dopaminergic perikaryon which present ascending axonal projections notably to the nucleus accumbens. This system, referred as the mesolimbic dopamine system has been demonstrated to display moderate to high density of enkephalin-containing fibers. This topographical analogy led us to evaluate the properties of kelatorphan, a new potent inhibitor of multiple enkephalin-degrading enzymes, on this mesolimbic system. Intracranial self-stimulation behavior served to estimate this mesolimbic dopaminergic function. Kelatorphan was injected either into the lateral ventricle or into the nucleus accumbens. Kelatorphan elicited opposite behavioral profiles, i.e. an intracranial self-stimulation increase when intracerebroventricularly injected (70 nmol) and a decreased self-stimulation behavior when directly administered into the nucleus accumbens (35 nmol). The results thus suggest that kelatorphan which protects endogenous enkephalins against enzymatic degradation seemed to act on the regulation of the mesolimbic dopamine system.
腹侧被盖区含有高密度的多巴胺能神经元胞体，其发出的轴突主要向上投射至伏隔核。这个系统，即中脑边缘多巴胺系统，已被证明含有中度至高密度的含脑啡肽纤维。这种拓扑学上的相似性促使我们评估新型强效多种脑啡肽降解酶抑制剂凯拉托芬对该中脑边缘系统的作用。颅内自我刺激行为用于评估该中脑边缘多巴胺能功能。将凯拉托芬注入侧脑室或伏隔核。凯拉托芬引发了相反的行为表现，即脑室内注射70纳摩尔时颅内自我刺激增加，而直接注入伏隔核35纳摩尔时自我刺激行为减少。因此，结果表明，能保护内源性脑啡肽免受酶解的凯拉托芬似乎作用于中脑边缘多巴胺系统的调节。
