GABAergic imbalance is normalized by dopamine D1 receptor activation in the striatum contralateral to the cortical injury in motor deficit-recovered rats
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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 D1 receptors (D1Rs) modulates the γ-aminobutyric acid (GABA) and glutamate levels in the striatum of recovered rats at 192 h after cortical injury.
The D1R 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 D1R mRNA on both sides of the striatum.
GABAergic imbalance in the striatum contralateral to the injury site was normalized by the administration of the D1R 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 D1R mRNA in the striatum contralateral to the injury, and this effect was blocked by the coadministration of the D1R antagonist SCH-23390 (2 mg/kg). In the striatum ipsilateral to the injury, the D1R agonist increased the D1R 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 D1R activation, and the D1R agonist-induced increases in the D1R mRNA levels in the striatum ipsilateral to the injury suggest that the striatum may be necessary to achieve functional recovery.
KeywordsDopamine D1 receptors Striatum GABA Glutamate Cortical injury mRNA
dopamine D1 receptor
dopamine D2 receptor
medium spiny neurons
traumatic brain injury
substantia nigra pars compacta
primary motor cortex
high-performance liquid chromatography
protein kinase A
DA- and cAMP-regulated phosphoprotein 32
We thank MVZ Hugo Lecona Butrón for the support with the housing, care, maintenance, and monitoring the health of the experimental animals in the INR-LGII. We thank MVZ Javier Pérez Gallaga and M en C René Valdez Mijares for technical support.
This work was supported by INR-LGII, CONACyT (grant 288512 to A. Avila-Luna).
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