Proconvulsive effect of hydrochlorothiazide in an in vitro rat seizure model

Objective(s):Protective effects of diuretics, particularly of hydrochlorothiazide (HCT), for the development of seizure attacksepilepsy have been described in vivo. However, itsthe mechanism of action of HCT is unknownneeds to be elucidated. Materials and Methods: Extracellular field potentials were recorded from the CA۱- and CA۳-subfields of the hippocampus of rats. Epileptiform discharges were induced by omission of Mg۲+ from the artificial cerebrospinal fluid (ACSF). HCT was added to the ACSF at a concentration of ۲ mmol/l (n=۵), ۰.۲ mmol/l (n=۵) or ۰.۰۲ mmol/l (n=۵). Frequency, amplitude and duration of the epileptiform discharges were evaluated. Long-term potentiation (LTP) was induced with and without the presence of HCT (n=۶; ۲ mmol/l). In addition, rats were injected with HCT (n=۴) or saline (n=۲), and the brain tissue was analyzed using HPLC. Results: Application of ۰.۰۲, ۰.۲, and ۲ mmol/l HCT accelerated the frequency of discharges by ۵۰%, ۹۱%, and ۱۰۰%, respectively. The amplitude of burst discharges also increased by ۹%, ۵۴%, and ۳۰۰%, and the duration of epileptiform discharges increased by ۱۰%, ۳۰% and ۱۲۰%. All parameters returned close to the basal levels after ۶۰min washout of the substance. HCT increased the electrical evoked potentials but did not affect the LTP in hippocampal tissues. There was no evidence of HCT in the rat brain after intraperitoneal injection. Conclusion: Exposure of hippocampal slices to HCT enhanced epileptiform activity in a dose-dependent manner. In addition, HCT does not seem to cross the blood brain barrier in rats. Thus, the anticonvulsive effect of HCT most likely is not through direct neuronal effect.

Keywords:

Blood-brain-barrier , Diuretics , Epilepsy , Hippocampal slices