Diurnal variation in the proconvulsant effect of 3-mercaptopropionic acid and the anticonvulsant effect of androsterone in the Syrian hamster

Abstract

GABA is the principal neurotransmitter of the mammalian circadian system, and its activity is subject to diurnal and circadian variations, with maximal values in hypothalamic turnover, content and binding during the night. In this study we have examined rhythms in the proconvulsant effect of inhibition of glutamate decarboxylase (GAD) in hamsters ( Mesocricetus auratus) as well as the anticonvulsant effect of androsterone, a neurosteroid that positively modulates the GABA A receptor. Administration of 10-60 mg/Kg of 3-mercaptopropionic acid (3-MPA, a GAD inhibitor) induced convulsions that were analyzed by an ad-hoc severity scale, with a lower sensitivity threshold at 24:00 h. Moreover, the latency for first and maximal convulsive response times was significantly lower at night. A similar temporal profile (maximal effect at midnight) was found for picrotoxin-induced seizures. Androsterone (40 mg/Kg) completely inhibited 3-MPA-induced tonic/clonic seizures at 12:00 h, while it had a partial inhibitory effect at 24:00 h. These results support the importance of temporal regulation of GABAergic modulation in the central nervous system.