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The role of dopamine receptors in mediating the effects of deep brain stimulation on seizure severity and learning and memory impairment in a laboratory model of seizures
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Mahmoud Rezaei   , Azam Sadeghian , Zahra Salari , Amir Shojaei , Javad Mirnajafi-Zadeh |
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Abstract: (240 Views) |
Introduction: Deep brain stimulation (DBS) has gained attention as a novel therapeutic approach for patients with refractory epilepsy, but its mechanism of action is not fully understood. DBS may exert its anti-seizure effects by modulating the function of certain neuromodulators such as dopamine. In this study, the role of dopamine receptors in mediating the effects of DBS on seizure severity and learning and memory impairment in a kindling model of seizures was investigated.
Methods and Materials: First, a chemical kindling model using pentylenetetrazol (PTZ) or electrical kindling was induced in animals. In the DBS treating groups, DBS with tonic (1 Hz) or phasic (100 Hz) patterns was applied to the ventral tegmental area (VTA) of animals at 5 minutes, 6, 24, and 30 hours after the last kindling stimulation or PTZ injection. Its effects on seizure severity, learning and memory (in Barnes and Y-maze tests), kindling-induced potentiation, and synaptic currents in the CA1 hippocampal region were examined.
Results: Only stimulation with tonic pattern showed anti-seizure effects. Tonic stimulation reduced the working memory impairment in kindled animals and restored the changes in synaptic inhibitory and excitatory currents in pyramidal neurons of the ventral hippocampal region to control values. These effects were not observed when haloperidol was injected intraventricularly into brain before tonic stimulation.
Conclusion: Tonic pattern stimulation in the VTA has anti-seizure effects and improves seizure-induced impairment in learning and memory. At least a part of these effects is mediated through the activation of D2-like dopamine receptors.
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| Keywords: epilepsy, seizure, deep brain stimulation, dopamine receptors, ventral tegmental area |
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Full-Text [PDF 263 kb]
(35 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2024/02/21 | Accepted: 2023/08/10 | Published: 2023/08/10
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