Kalyuzhny A E, Wessendorf M W
Department of Cell Biology and Neuroanatomy, University of Minnesota, Minneapolis 55455, USA.
J Comp Neurol. 1998 Mar 23;392(4):528-47.
Inhibition of neurons containing gamma-aminobutyric acid (GABA) may underlie some of the excitatory effects of opioids in the central nervous system (CNS). In the present study, we examined the relationship of the cloned mu- and delta-opioid receptors (MOR1 and DOR1, respectively) to GABAergic neurons in brain and spinal cord. This was done by combining immunofluorescent staining for MOR1 or DOR1 with that for GABA or glutamic acid decarboxylase (GAD); fluorescent retrograde tract-tracing was used in some cases to identify neurons with particular projections. In rats, cells double labeled for GABA and MOR1 were observed in layers II-VI of the parietal cortex and in layers II-IV of the piriform cortex. In the hippocampus, double labeling was observed in the dentate gyrus and in regions CA1 and CA3. Double labeling was very prominent in the striatum and in the reticular nucleus of the thalamus; it was also observed in other portions of the diencephalon. However, double labeling for GABA and MOR1 was never observed in the cerebellar cortex. Cells double labeled for GABA and MOR1 were common in the periaqueductal gray (PAG) and the medial rostral ventral medulla (RVM) of both rats and monkeys, suggesting that involvement of GABAergic neurons with supraspinal opioid antinociception may extend to primates. In the RVM of rats, many of those double-labeled neurons were retrogradely labeled from the dorsal spinal cord. In contrast, double-labeled neurons in the PAG were almost never retrogradely labeled from the RVM. No unequivocal examples of double labeling for DOR1 and GAD were found in any region of the CNS that we examined in either rats or monkeys. However, GABAergic neurons were often apposed by DOR1 immunoreactive varicosities. Our findings suggest that activation of mu-opioid receptors directly modulates the activity of GABAergic neurons throughout the CNS, including neurons involved in the supraspinal component of opioid analgesia. In contrast, delta-opioid receptors appear to be positioned to modulate the activity of GABAergic neurons indirectly.
抑制含γ-氨基丁酸（GABA）的神经元可能是阿片类药物在中枢神经系统（CNS）产生某些兴奋作用的基础。在本研究中，我们检测了克隆的μ-和δ-阿片受体（分别为MOR1和DOR1）与脑和脊髓中GABA能神经元的关系。这是通过将MOR1或DOR1的免疫荧光染色与GABA或谷氨酸脱羧酶（GAD）的免疫荧光染色相结合来完成的；在某些情况下使用荧光逆行束路追踪来识别具有特定投射的神经元。在大鼠中，在顶叶皮质的II - VI层和梨状皮质的II - IV层观察到GABA和MOR1双重标记的细胞。在海马体中，在齿状回以及CA1和CA3区域观察到双重标记。双重标记在纹状体和丘脑网状核中非常明显；在间脑的其他部分也观察到了。然而，在小脑皮质中从未观察到GABA和MOR1的双重标记。在大鼠和猴子的导水管周围灰质（PAG）和延髓头端腹内侧区（RVM）中，GABA和MOR1双重标记的细胞很常见，这表明GABA能神经元参与脊髓上阿片类镇痛作用可能延伸至灵长类动物。在大鼠的RVM中，许多这些双重标记的神经元从背侧脊髓被逆行标记。相比之下，PAG中的双重标记神经元几乎从未从RVM被逆行标记。在我们检测的大鼠或猴子中枢神经系统的任何区域，均未发现DOR1和GAD双重标记的确切例子。然而，GABA能神经元常常与DOR1免疫反应性曲张体相邻。我们的研究结果表明，μ-阿片受体的激活直接调节整个中枢神经系统中GABA能神经元的活性，包括参与阿片类镇痛脊髓上成分的神经元。相比之下，δ-阿片受体似乎是通过间接方式来调节GABA能神经元的活性。
