Hippocampal Afterdischarges after GABAB‐Receptor Blockade in the Freely Moving Rat

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Abstract
Summary: Purpose: To determine whether hippocampal afterdischarges (ADs) and excitability changes were induced by γ-aminobutyric acid (GABA)B-receptor blockade in adult, freely moving rats. Methods: A specific GABAB-receptor antagonist CGP35348, CGP55845A, or CGP55699A was injected intracerebroventricularly (i.c.v.), and EEGs and behaviors of rats were analyzed. Results: CGP35348 (56–110 μg, i.c.v.) induced afterdischarges (ADs) ∼60% of the time, starting at the hippocampus or neocortex. Neocortical-onset ADs began with sporadic discharges and were 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 Conclusions: GABAB-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.