Hippocampal afterdischarges after GABA(B)-receptor blockade in the freely moving rat.

PURPOSE

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.