Lab. Neurofisiología Química de la Discapacidad, División de Neurociencias, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, SSa, Calz. México-Xochimilco 289, Col. Arenal de Guadalupe, 14389, Mexico City, Mexico.
Departamento de Genética y Medicina Genómica, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, SSa, Calz. México-Xochimilco 289, Col. Arenal de Guadalupe, 14389, Mexico City, Mexico.
Psychopharmacology (Berl). 2019 Jul;236(7):2211-2222. doi: 10.1007/s00213-019-05215-1. Epub 2019 Mar 11.
The sensorimotor cortex and the striatum are interconnected by the corticostriatal pathway, suggesting that cortical injury alters the striatal function, which may be modulated by dopamine.
We studied whether the activation of dopamine D receptors (DRs) modulates the γ-aminobutyric acid (GABA) and glutamate levels in the striatum of recovered rats at 192 h after cortical injury.
The DR agonist SKF-38393 (0, 2, 3, or 4 mg/kg) was administered at 24, 48, 96, and 192 h post-injury, and then rats were decapitated to determine GABA and glutamate levels and the levels of DR mRNA on both sides of the striatum.
GABAergic imbalance in the striatum contralateral to the injury site was normalized by the administration of the DR agonist, but this treatment did not produce a significant effect on glutamate levels, suggesting that glutamate was metabolized into GABA. The administration of SKF-38393 (2 mg/kg) decreased the levels of DR mRNA in the striatum contralateral to the injury, and this effect was blocked by the coadministration of the DR antagonist SCH-23390 (2 mg/kg). In the striatum ipsilateral to the injury, the DR agonist increased the DR mRNA levels, an effect that was blocked by SCH-23390.
The reversal of the GABAergic imbalance in the striatum contralateral to the cortical injury can be modulated by extrastriatal DR activation, and the DR agonist-induced increases in the DR mRNA levels in the striatum ipsilateral to the injury suggest that the striatum may be necessary to achieve functional recovery.
感觉运动皮层和纹状体通过皮质纹状体通路相互连接，这表明皮质损伤改变了纹状体的功能，而多巴胺可能对此进行调节。
我们研究了多巴胺 D 受体 (DR) 的激活是否会调节皮质损伤后 192 小时恢复大鼠纹状体中的γ-氨基丁酸 (GABA) 和谷氨酸水平。
在损伤后 24、48、96 和 192 小时，给予 DR 激动剂 SKF-38393(0、2、3 或 4mg/kg)，然后处死大鼠以确定纹状体两侧的 GABA 和谷氨酸水平以及 DR mRNA 水平。
DR 激动剂的给药使损伤侧纹状体的 GABA 能失衡得到正常化，但这种治疗对谷氨酸水平没有产生显著影响，表明谷氨酸被代谢为 GABA。SKF-38393(2mg/kg)的给药降低了损伤对侧纹状体中 DR mRNA 的水平，而这种作用被 DR 拮抗剂 SCH-23390(2mg/kg)的共同给药所阻断。在损伤侧纹状体中，DR 激动剂增加了 DR mRNA 水平，这种作用被 SCH-23390 阻断。
皮质损伤对侧纹状体 GABA 能失衡的逆转可以通过纹状体外 DR 激活来调节，而 DR 激动剂诱导损伤对侧纹状体 DR mRNA 水平的增加表明纹状体可能是实现功能恢复所必需的。
