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

The mechanisms involved in the anti-seizure effects of low-frequency stimulation (LFS) have not been completely determined. However, Gi-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.

Spatial Learning and Memory in Barnes Maze Test and Synaptic Potentiation in Schaffer Collateral-CA1 Synapses of Dorsal Hippocampus in Freely Moving Rats.

INTRODUCTION: Synaptic plasticity has been suggested as the primary physiological mechanism underlying memory formation. Many experimental approaches have been used to investigate whether the mechanisms underlying Long-Term Potentiation (LTP) are activated during learning. Nevertheless, little evidence states that hippocampal-dependent learning triggers synaptic plasticity. In this study, we investigated if learning and memory in the Barnes maze test are accompanied by the occurrence of LTP in Schaffer collateral to CA1 synapses in freely moving rats. METHODS: The rats were implanted with a recording electrode in stratum radiatum and stimulating electrodes in Schaffer collaterals of the CA1 region in the dorsal hippocampus of the right hemisphere. Following the recovery period of at least 10 days, field potentials were recorded in freely moving animals before and after training them in Barnes maze as a hippocampal-dependent spatial learning and memory test. The slope of extracellular field Excitatory Postsynaptic Potentials (fEPSPs) was measured before and after the Barnes maze test. RESULTS: The results showed that the fEPSP slope did not change after learning and memory in the Barnes maze test, and this spatial learning did not result in a change in synaptic potentiation in the CA1 region of the hippocampus. CONCLUSION: Spatial learning and memory in the Barnes maze test are not accompanied by LTP induction in Schaffer collateral-CA1 synapses.

Antiepileptic and Antioxidant Effect of Brassica nigra on Pentylenetetrazol-Induced Kindling in Mice.

Considering the high rate of epilepsy today, with respect to the insufficiency of the available therapies, new strategies and methods are recommended for medical treatment of epileptic patients. Therefore, the present study experimentally investigated the anticonvulsant effect of a herbal medicine candidate brassica nigra, by using kindling method. Sixty male mice were randomly selected and divided into six experimental groups (n = 10) including: 1-control, 2-pentylentetrazole (PTZ)-kindled mice, 3-positive control group received valproate (100 mg/Kg) as anti-convulsant drug, 4-5 and 6 received brassica nigra seed extract in three doses (75, 150 and 300 mg/Kg; IP). All groups except for the control ones were kindled by 11 period injections of PTZ (35 mg/Kg; IP). In the 12th injection, all groups except for the control group were tested for PTZ challenge dose (75 mg/Kg). However, the exhibited phases of seizure (0-6) were observed and noted till 30 min after the PTZ injection. At last, the brains of all the mice were removed and then malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO) levels of the brain tissues were determined. Statistical analysis of the data shows that the seed extract could reduce the intensity, improvement and duration of seizure. In addition, the brassica nigra extract increased the SOD and NO levels and decreased the MDA level in the brain tissues. Attained results show that the extract of Brassica nigra seed can be used in grand mal seizure treatment. Moreover, the antiepileptic effect of this extract is probably caused by its antioxidant properties and acts via enzyme activity mechanism.