NEUROTOXICAL STUDIES ON FUMITREMORGIN-A, A TREMORGENIC MYCOTOXIN, ON MICE

A tremorgenic mycotoxin, fumitremorgin A (FTA) produces tremor and convulsive seizure, when injected intravenously. The intravenous LD50of this toxin was 0.185 mg/kg in mice. Neuropharmacologic agents known to be serotonergic, dopaminergic and GABAergic function in brain were used to investigate the possible relationship between these putative transmitter systems and the induction and modulation of FTA-induced tremor and tonic-clonic convulsion. The results indicate a non-involvement of dopaminergic function in central nervous system and a possible involvement of serotonergic and/or GABAergic function with FTA-induced neural signs. Dopaminergic agents, e. g. diethyldithiocarbamate, Ldopa, failed to modify tremor and convulsion; monoamine depleting agents, e. g. reserpine reduced tremor and convulsion; serotonin elevating agents, e. g. isocarboxazid plus L-tryptophan intensified FTA-induced tremor and convulsion. Modification of FTA-induced tremor and convulsion by some agents capable of elevating or decreasing GABA (aminooxyacetic acid, semicarbazide) was also observed. Furthermore, an elevation of serotonin (5-HT) and a decrease of GABA in FTA-treated mice were noted. These results obtained suggest a possible involvement of central serotonergic and/or GABAergic function with FTA-induced tremor and tonic-clonic convulsion. © 1979, The Pharmaceutical Society of Japan. All rights reserved.