Neurobehavioral Studies of Tremorgenic Mycotoxins Verruculogen and Penitrem A

Abstract

Verruculogen (V) and penitrem A (PA) represent a group of toxic secondary metabolites of mold contaminants of foodstuffs known as ‘tremorgenic mycotoxins’, which produce a unique neurotoxic syndrome characterized by sustained tremors, limb weakness, ataxia and convulsions. In the present study the intraperitoneal median tremorgenic dose in mice for V was found to be 0.92 mg/kg and that for PA, 0.19 mg/kg. Behavioral and neurochemical parameters were assessed following acute exposure to varying neurotoxic and subneurotoxic doses of these mycotoxins. Measures of spontaneous motor activity (photoactometer) and exploratory reflex behaviors (open field) were markedly depressed by both V and PA. Notably, at dose levels of V or PA that were not accompanied by any overt signs of neurotoxicity, significant neuromotor depression was still observed. Acquisition of a conditioned avoidance shuttle response was disrupted, but only at a high neurotoxic dose level of V. Neurochemical analyses revealed no clear catecholaminergic or cholinergic involvement in the neurotoxic syndrome of either V or PA.