학술논문
GABAergic imbalance is normalized by dopamine D.sub.1 receptor activation in the striatum contralateral to the cortical injury in motor deficit-recovered rats
Original Investigation
Original Investigation
Document Type
Academic Journal
Author
Source
Psychopharmacology. July 2019, Vol. 236 Issue 7, p2211, 12 p.
Subject
Language
English
ISSN
0033-3158
Abstract
Author(s): Arturo Gálvez-Rosas [sup.1] , Alberto Avila-Luna [sup.1] , Margarita Valdés-Flores [sup.2] , Sergio Montes [sup.3] , Antonio Bueno-Nava [sup.1] Author Affiliations: (Aff1) 0000 0004 0633 2911, grid.419223.f, Lab. Neurofisiología [...]
Rationale 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. Objectives We studied whether the activation of dopamine D.sub.1 receptors (D.sub.1Rs) modulates the [gamma]-aminobutyric acid (GABA) and glutamate levels in the striatum of recovered rats at 192 h after cortical injury. Methods The D.sub.1R 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 D.sub.1R mRNA on both sides of the striatum. Results GABAergic imbalance in the striatum contralateral to the injury site was normalized by the administration of the D.sub.1R 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 D.sub.1R mRNA in the striatum contralateral to the injury, and this effect was blocked by the coadministration of the D.sub.1R antagonist SCH-23390 (2 mg/kg). In the striatum ipsilateral to the injury, the D.sub.1R agonist increased the D.sub.1R mRNA levels, an effect that was blocked by SCH-23390. Conclusion The reversal of the GABAergic imbalance in the striatum contralateral to the cortical injury can be modulated by extrastriatal D.sub.1R activation, and the D.sub.1R agonist-induced increases in the D.sub.1R mRNA levels in the striatum ipsilateral to the injury suggest that the striatum may be necessary to achieve functional recovery.
Rationale 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. Objectives We studied whether the activation of dopamine D.sub.1 receptors (D.sub.1Rs) modulates the [gamma]-aminobutyric acid (GABA) and glutamate levels in the striatum of recovered rats at 192 h after cortical injury. Methods The D.sub.1R 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 D.sub.1R mRNA on both sides of the striatum. Results GABAergic imbalance in the striatum contralateral to the injury site was normalized by the administration of the D.sub.1R 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 D.sub.1R mRNA in the striatum contralateral to the injury, and this effect was blocked by the coadministration of the D.sub.1R antagonist SCH-23390 (2 mg/kg). In the striatum ipsilateral to the injury, the D.sub.1R agonist increased the D.sub.1R mRNA levels, an effect that was blocked by SCH-23390. Conclusion The reversal of the GABAergic imbalance in the striatum contralateral to the cortical injury can be modulated by extrastriatal D.sub.1R activation, and the D.sub.1R agonist-induced increases in the D.sub.1R mRNA levels in the striatum ipsilateral to the injury suggest that the striatum may be necessary to achieve functional recovery.