The role of dopamine D2-like receptors in a "depotentiation-like effect" of deep brain stimulation in kindled rats

Abstract

The mechanisms involved in the anti-seizure effects of low-frequency stimulation (LFS) have not been completely determined. However, G_i-protein-coupled receptors, including D₂-like receptors, may have a role in mediating these effects. In the present study, the role of D₂-like receptors in LFS' anti-seizure action was investigated. Rats were kindled with semi-rapid (6 stimulations per day), electrical stimulation of the hippocampal CA1 area. In LFS-treated groups, subjects received four trials of LFS at 5 min, 6 h, 24 h, and 30 h following the last kindling stimulation. Each LFS set occurred at 5 min intervals, and consisted of 4 trains. Each train contained 200, 0/1 ms long, monophasic square wave pulses at 1 Hz. Haloperidol (D₂-like receptors antagonist, 2 µm) and/or bromocriptine (D₂-like receptors agonist 2 µg/µlit) were microinjected into the lateral ventricle immediately after the last kindling, before applying LFS. Obtained results showed that applying LFS in fully-kindled subjects led to a depotentiation-like decrease in kindling-induced potentiation and reduced the amplitude and rise slope of excitatory and inhibitory post-synaptic currents in whole-cell recordings from CA1 pyramidal neurons. In addition, LFS restored the kindling-induced, spatial learning and memory impairments in the Barnes maze test. A D₂-like receptor antagonist inhibited these effects of LFS, while a D₂-like receptor agonist mimicked these effects. In conclusion, a depotentiation-like mechanism may be involved in restoring LFS' effects on learning and memory, and synaptic plasticity. These effects depend on D₂-like receptors activity.

Keywords: Deep brain frequency stimulation; Dopamine D(2) receptors; Learning and memory; Seizure; Synaptic plasticity.