The role of 5-HT1A receptors of hippocampal CA1 region in anticonvulsant effects of low-frequency stimulation in amygdala kindled rats

Physiol Behav. 2018 Nov 1:196:119-125. doi: 10.1016/j.physbeh.2018.08.025. Epub 2018 Sep 1.

Abstract

Low frequency stimulation (LFS) has been proposed as a method in the treatment of epilepsy, but its anticonvulsant mechanism is still unknown. In the current study, the hippocampal CA1 region was microinjected with NAD-299 (a selective 5-HT1A antagonist), and its role in mediating the inhibitory action of LFS on amygdala kindling was investigated. Male Wistar rats were kindled by amygdala stimulation in a semi-rapid kindling manner (12 stimulations per day). LFS (0.1 ms pulse duration at 1 Hz, 200 pulses, 50-150 μA) was applied at 5 min after termination of daily kindling stimulations. NAD (a selective 5-HT1A antagonist) was microinjected into the CA1 region of the hippocampus at the doses of 2.5 and 5 μg/1 μl. An open field test was also run to determine the motor activity of animals in different experimental groups. The application of LFS following daily kindling stimulations reduced the behavioral seizure stages, afterdischarge duration, and stage 5 seizure duration and increased the latency to stage 4 seizure compared to the kindled group. However, microinjection of NAD at the doses of 5 μg/1 μl, but not 2.5 μg/1 μl, blocked the inhibitory effect of LFS on behavioral and electrophysiological parameters in kindled animals. It could be presumed that 5-HT1A receptors in the CA1 area are involved in mediating the antiepileptic effects of LFS.

Keywords: 5-HT(1A) receptor; Brain stimulation; Hippocampus; Kindling; Seizure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / drug effects
  • Amygdala / metabolism
  • Animals
  • Benzopyrans / pharmacology
  • CA1 Region, Hippocampal / drug effects
  • CA1 Region, Hippocampal / metabolism*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Electric Stimulation Therapy*
  • Implantable Neurostimulators
  • Kindling, Neurologic
  • Male
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Seizures / metabolism*
  • Seizures / therapy*
  • Serotonin 5-HT1 Receptor Antagonists / pharmacology

Substances

  • Benzopyrans
  • Serotonin 5-HT1 Receptor Antagonists
  • Receptor, Serotonin, 5-HT1A
  • robalzotan