Neurobehavioral effects of permethrin are associated with alterations in regional levels of biogenic amine metabolites and amino acid neurotransmitters

Abstract

Oral administration of 120 or 240 mg/kg permethrin produced dose- and time-related tremor in rats with the peak effect occurring 5 hrs after dosing. Subsequent experiments done 5 hrs postdosing found that 45 to 180 mg/kg permethrin produced dose-related increases in rectal temperature and enhanced responsiveness to an acoustic stimulus. Tremor was detected at 90 and 180 mg/kg. Neurochemical analyses of regional biogenic amines and their metabolites and amino acids 5 hrs after 90 or 180 mg/kg indicated that 5-HIAA levels were increased in the hypothalamus (HYP), brain stem (BS), hippocampus (HPC), and striatum (STR); 5-HT was not affected. MHPG was increased in the HYP and BS, while NE was decreased at the high dose only. DOPAC and HVA were increased in the STR after 90 and 180 mg/kg, while DA was not affected. Aspartate levels were increased in the BS and STR; glutamate was increased in the BS. Taurine, glutamine, glycine, and GABA were not affected. A time-course analysis of neurochemical changes 2, 5, 12, and 24 hrs postdosing indicated that 5 hrs was the time of peak effect for permethrin. Permethrin-induced tremor and hyperthermia were significantly correlated with dose- and time-related changes in MHPG, 5-HIAA, and ASP.