Abstracts

Protective effects of diuretics, particularly of hydrochlorothiazide (HCT), for the development of seizures attacks were described. An anticonvulsive effect of furosemide and HCT was also found in several animal models of epilepsy. Whereas furosemide most likely exerts its antiepileptic effect directly by blocking ion transporters in neurons, the anticonvulsive mechanism of HCT needs to be elucidated. We intended to examine the effect of HCT in an in-vitro model of epilepsy. Extracellular field potentials were recorded from the CA1- and CA3-subfields of the hippocampus of rats. Epileptiform discharges were induced by omission of Mg²⁺ from the artificial cerebrospinal fluid (ACSF). After obtaining a stable frequency and amplitude of the discharges, HCT was added to the ACSF at a concentration of 2mmol/l (n=5), 0.2mmol/l (n=5) or 0.02 mmol/l (n=5). After 60 minutes of exposure, a wash-out phase of 60 minutes followed. Frequency, amplitude and duration of the epileptiform discharges were evaluated. Long-term potentiation (LTP) was induced by tetanic stimulations applied to Schaffer collaterals with and without the presence of HCT (n = 6; 2 mmol/l). Application of HCT, in a dose dependent manner, enhanced epileptiform activity. Repetition rate, amplitude, and duration of epileptiform burst discharges reversibly increased by drug administration. Application of 0.02. 0.2, and 2 mmol/l HCT accelerated the frequency of discharges by 50%, 91%, and 100%, respectively. The amplitude of burst discharges also increased by 9%, 54%, and 300% and the duration of epileptiform discharges increased by 10%, 30% and 120% during application of 0.02. 0.2, and 2 mmol/l HCT, respectively. All parameter returned to the basal levels after 60min washout of the substance. HCT increased the electrical evoked potentials but did not affect the LTP in hippocampal tissues. Although HCT seems to have anticonvulsive properties in vivo, exposure of hippocampal slices to HCT results enhanced the epileptiform activitiy in a dose-dependent manner. Thus, the anticonvulsive effect of HCT most likely is not through direct neuronal inhibition.