The effects of GABA B receptor activation on spontaneous and evoked activity in the dentate gyrus of kainic acid-treated rats

Abstract

Enhancement of GABAergic inhibition is central to the treatment of epilepsy. The role of the GABA B receptor, however, is poorly understood. The current study investigates the effects of r-baclofen (a GABA B receptor agonist) on spontaneous and evoked electrophysiological activity in the dentate gyrus of normal and epileptic rats in vivo. Administration of kainic acid (KA), which causes similar pathology to that seen in human temporal lobe epilepsy, was used to prepare chronically epileptic rats. Bursts of spontaneous high-amplitude field potentials (spiking) were observed in isoflurane-anaesthetised control and KA-treated rats in vivo; however, this activity was significantly more frequent in KA-treated rats (223±26.1 spikes min −1) than in control rats (124±17.4 spikes min −1). Feedback inhibition, measured using paired-pulsed stimulation, was also greater in KA-treated rats; 50% inhibition of the second response was observed at 43.05±4.46 ms in KA-treated animals, as opposed to 26.27±2.39 ms in control animals. r-Baclofen (10 mg kg −1 i.v.) abolished spontaneous spiking and also reduced feedback inhibition in both control and KA-treated rats. These effects of r-baclofen may be due to inhibition of GABA release, through activation of pre-synaptic GABA B receptors on terminals of interneurones in the inhibitory feedback pathway. These results suggest a link between feedback inhibition and spontaneous spiking, and provide support for the hypothesis that mechanisms of synchronisation may give rise to seizure activity in human temporal lobe epilepsy.