Hippocampal afterdischarges after GABA(B)-receptor blockade in the freely moving rat.
OBJECTIVE
To determine whether hippocampal afterdischarges (ADs) and excitability changes were induced by gamma-aminobutyric acid (GABA)(B)-receptor blockade in adult, freely moving rats.


METHODS
A specific GABA(B)-receptor antagonist CGP35348, CGP55845A, or CGP55699A was injected intracerebroventricularly (i.c.v.), and EEGs and behaviors of rats were analyzed.


RESULTS
CGP35348 (56-110 microg, i.c.v.) induced afterdischarges (ADs) approximately 60% of the time, starting at the hippocampus or neocortex. Neocortical-onset ADs began with sporadic discharges and were <3 mV. Hippocampal-onset ADs were bilateral, >5 mV, and spread to the entorhinal cortex and amygdala, often ending in a rebound AD and accompanied with stereotypic jumping, forelimb clonus, and wet-dog shakes. The CGP35348-induced hippocampal AD had an onset frequency (5-9 Hz) that was higher than the electrically evoked AD (2-4 Hz). CGP35348 i.c.v. also increased the mean starting frequency of an electrically evoked hippocampal AD from 3.6 Hz to 5.3 Hz. Hippocampal gamma activity (25-80 Hz) increased up to twofold for 30 min after a hippocampal but not a neocortical AD. A single dose of CGP35348 induced repeated ADs of increasing duration. Paired-pulse inhibition of the evoked potentials in CA1, at interpulse interval of <100 ms, was decreased after but not before a hippocampal AD. CGP56999A (i.c.v.) gave results similar to those with CGP35348, whereas CGP55845A (i.c.v.) rarely induced ADs.


CONCLUSIONS
GABA(B)-receptor blockade increases seizure susceptibility by reducing AD threshold and increasing the frequency and spread of a hippocampal AD. Hippocampal excitability (based on paired-pulse test) and gamma activity increased after but not before a hippocampal AD.
Leung
L Stan
LS
Department of Physiology-Pharmacology, University of Western Ontario, London, Ontario, Canada. sleung@uwo.ca
Canning
Kevin J
KJ
Shen
Bixia
B
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D058788:GABA-B Receptor Antagonists; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007278:Injections, Spinal; D007696:Kindling, Neurologic / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D019579:Neocortex / Q000187:drug effects / Q000502:physiology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D012640:Seizures / Q000139:chemically induced*; D013826:Theta Rhythm / Q000187:drug effects
D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; C066430:CGP 35348