» Articles » PMID: 34331457

Anticonvulsant Dopamine Type 2 Receptor Agonist Activates Inhibitory Parvalbumin Interneurons

Overview
Journal Epilepsia
Specialty Neurology
Date 2021 Jul 31
PMID 34331457
Citations 5
Authors
Affiliations
Soon will be listed here.
Abstract

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.

Citing Articles

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.


How dopamine tunes parvalbumin interneurons in the hippocampus: new experimental observations in Alzheimer's disease.

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.


Dopamine neuron degeneration in the Ventral Tegmental Area causes hippocampal hyperexcitability in experimental Alzheimer's Disease.

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.


In Silico Analysis, Anticonvulsant Activity, and Toxicity Evaluation of Schisandrin B in Zebrafish Larvae and Mice.

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.

References
1.
Brodovskaya A, Shiono S, Kapur J . Activation of the basal ganglia and indirect pathway neurons during frontal lobe seizures. Brain. 2021; 144(7):2074-2091. PMC: 8502464. DOI: 10.1093/brain/awab119. View

2.
Hu H, Gan J, Jonas P . Interneurons. Fast-spiking, parvalbumin⁺ GABAergic interneurons: from cellular design to microcircuit function. Science. 2014; 345(6196):1255263. DOI: 10.1126/science.1255263. View

3.
Centonze D, Grande C, Usiello A, Gubellini P, Erbs E, Martin A . Receptor subtypes involved in the presynaptic and postsynaptic actions of dopamine on striatal interneurons. J Neurosci. 2003; 23(15):6245-54. PMC: 6740558. View

4.
Singh T, Joshi S, Williamson J, Kapur J . Neocortical injury-induced status epilepticus. Epilepsia. 2020; 61(12):2811-2824. PMC: 8764937. DOI: 10.1111/epi.16715. View

5.
Li K, Lu Y, Xu Z, Zhang J, Zhu J, Zhang J . Neuregulin 1 regulates excitability of fast-spiking neurons through Kv1.1 and acts in epilepsy. Nat Neurosci. 2011; 15(2):267-73. DOI: 10.1038/nn.3006. View