Intrahippocampal 5-HT receptor antagonist inhibits the improving effect of low-frequency stimulation on memory impairment in kindled rats.

In addition to its anticonvulsant effect, low frequency stimulation (LFS) improves learning and memory in kindled animals. In the present study, the role of 5-HT receptors in mediating LFS' improving effect on spatial learning and memory was investigated in amygdala-kindled rats. Amygdala kindling was conducted in a semi-rapid kindling stimulations (12 stimulations per day) in male Wistar rats. LFS (4 trains of 0.1 ms pulse duration at 1 Hz, 200 pulses, 50-150 μA, at 5 min intervals) was applied after termination of kindling stimulations. NAD-299 (a selective 5-HT receptor antagonist; 2.5 and 5 μg/μl) was microinjected into the hippocampal CA1 before applying LFS. The Morris water maze, and novel object recognition tests were conducted after the last kindling stimulation. Hippocampal samples were also prepared, and 5-HT receptor gene expression levels were assessed using quantitative RT-PCR. In kindled animals, LFS reduced impairments in spatial learning and memory in the Morris water maze and novel object recognition tests. Microinjection of NAD doses of 5 μg/μl reduced the effects of LFS on learning and memory. The gene expression level of 5-HT receptors increased significantly in the hippocampus of amygdala-kindled rats. However, LFS applied after kindling stimulations inhibited this effect. It seems that activation of 5-HT receptors in the CA1 field is necessary for LFS' improving effects on spatial learning and memory in kindled animals; although surprisingly, LFS application prevented the elevation in gene expression of 5-HT receptors in kindled animals.