title: Hippocampal melatonin receptors modulate seizure threshold.
abstract: OBJECTIVE
  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.
authors.affiliation: Program in Neuroscience, Department of Physiology & Pharmacology, The University of Western Ontario, London, Ontario, Canada. lee.stewart@mcgill.ca
authors.forename: Lee S
authors.initials: LS
authors.lastname: Stewart
authors.forename: L Stan
authors.initials: LS
authors.lastname: Leung
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000187:drug effects / Q000706:statistics & numerical data; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D044094:Receptors, Melatonin / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000502:physiology; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014363:Tryptamines / Q000494:pharmacology
chemical_list: C114459:4-phenyl-2-propionamidotetraline; D018756:GABA Antagonists; D044094:Receptors, Melatonin; D013764:Tetrahydronaphthalenes; D014363:Tryptamines; D010862:Pilocarpine; C057154:luzindole; D009118:Muscimol