Hippocampal melatonin receptors modulate seizure threshold.

Abstract:

PURPOSE:The pineal hormone melatonin has been shown to enhance hippocampal excitability. We therefore investigated whether inactivation of hippocampal melatonin receptors affects behavioral seizures. METHODS:Intrahippocampal infusions were performed in rats to study the effect of different melatonin receptor antagonists on behavioral activity, EEG, and seizure susceptibility. Experiments were conducted at 2 times of the day that coincided with the peak and trough of the daily melatonin rhythm. RESULTS:Local infusion of the Mel(1b) receptor antagonist 4-phenyl-2-propionamidotetralin (4-P-PDOT) into the hippocampus, but not the overlying neocortex, significantly increased seizure latency and in some cases provided complete protection against seizure development. In addition, 4-P-PDOT suppressed open field activity and hippocampal EEG amplitude. The mixed Mel(1a)/Mel(1b) receptor antagonist luzindole also increased seizure latency but to a lesser degree than 4-P-PDOT. The behavioral effects of Mel(1b) receptor inhibition were comparable to those of the gamma-aminobutyric acid (GABA)(A) receptor agonist muscimol and were observed during the dark phase (2400-0200 h) but not the light phase (1200-1400 h) of the daily photocycle. The anticonvulsant effect of intrahippocampal infusion of 4P-P-DOT was blocked by coadministration of the GABA(A) antagonist bicuculline. CONCLUSIONS:Our results suggest that nocturnal activation of hippocampal Mel(1b) receptors depresses GABA(A) receptor function in the hippocampus and enhances seizure susceptibility.

journal_name

Epilepsia

journal_title

Epilepsia

authors

Stewart LS,Leung LS

doi

10.1111/j.0013-9580.2005.30204.x

subject

Has Abstract

pub_date

2005-04-01 00:00:00

pages

473-80

issue

4

eissn

0013-9580

issn

1528-1167

pii

EPI30204

journal_volume

46

pub_type

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