Anticonvulsant Dopamine Type 2 Receptor Agonist Activates Inhibitory Parvalbumin Interneurons
Authors
Affiliations
Dopamine type 2 receptor (D2R) agonists have anticonvulsant effect, whereas D2R antagonists increase seizure risk, but the mechanism of this action has not been delineated. We tested whether D2R agonists activate parvalbumin (PV)-containing inhibitory interneurons to suppress seizures. We treated frontal lobe onset seizures with a D2R agonist sumanirole, and it suppressed seizures. We used activity reporter TRAP2 mice and found that injection of D2R agonist led to extensive activation of PV interneurons in the cortex and striatum ipsilateral to the seizure focus. D2R agonists activate PV interneurons, which in turn inhibit principal neurons, potentially explaining their anticonvulsant effect.
Dopamine Dilemma Overexcites the Hippocampus in Alzheimer's Disease.
Wong J Epilepsy Curr. 2024; 24(5):361-363.
PMID: 39508014 PMC: 11536398. DOI: 10.1177/15357597241280475.
La Barbera L, Krashia P, Nobili A Neural Regen Res. 2024; 20(5):1405-1406.
PMID: 39075905 PMC: 11624865. DOI: 10.4103/NRR.NRR-D-24-00322.
Spoleti E, La Barbera L, Cauzzi E, De Paolis M, Saba L, Marino R Mol Psychiatry. 2024; 29(5):1265-1280.
PMID: 38228889 PMC: 11189820. DOI: 10.1038/s41380-024-02408-9.
Nieoczym D, Banono N, Stepnik K, Kaczor A, Szybkowski P, Esguerra C Int J Mol Sci. 2023; 24(16).
PMID: 37629132 PMC: 10455331. DOI: 10.3390/ijms241612949.
Nucleus accumbens shell modulates seizure propagation in a mouse temporal lobe epilepsy model.
Zou W, Guo Z, Suo L, Zhu J, He H, Li X Front Cell Dev Biol. 2023; 10:1031872.
PMID: 36589737 PMC: 9797862. DOI: 10.3389/fcell.2022.1031872.