Thiosemicarbazide (TIO) is a hydrazyde inhibitor of brain glutamate descarboxylase that induces tonic-clonic seizures and death. This effect is associated with the sharp deficiency produced in the central GABAergic function but because a lesser marked reduction could induce anxiety related behaviors we probe the effect of subconvulsive doses on differents anxiety tests to know the anxiogenic outline of this inhibitor. Groups of adult Wistar rats were administered i.p. with 0, 0.03, 0.11, 0.34 or 3.4 mg/kg of TIO. Tests were made two hours after injection and consisted in locomotor activity in open field (OF) and rotarod test (R) as measures of motor activity whereas defensive burying behavior (DBB), social interaction (SI) and elevated plus maze (EPM) tests were used as measures of anxiety using rats in only one anxiety test to prevent inter-tests effects. Results showed that 0.34 and 3.4 mg/kg had a depressor effect on motor activity in OF and R that did not allow to make the anxiety tests. At 0.03 and 0.11 mg/kg the locomotor activity in OP did not show any change and the motor performance in rotarod was slightly affected at 0.11 mg/kg. This same dose increased the burying time (DBB) and reduced the interaction time (SI) and the open arm time (EPM). In DBB the anxiogenic effect was efectively antagonized with diazepam (1mg/kg). These results prove that TIO can be used as an anxiogenic agent with a broad profile in anxiety tests.

Supported by: fellowships by EDD and COFAA; Grant CGPI 20070521