DOMOIC ACID - NEUROBEHAVIORAL AND NEUROHISTOLOGICAL EFFECTS OF LOW-DOSE EXPOSURE IN ADULT-RATS

Adult rats treated IP with domoic acid at 0, 0.22, 0.65, or 1.32 mg/kg were tested for passive avoidance (PA), auditory startle (AS), or con ditioned avoidance (CAR) behaviors. Clinical signs were observed only at the 1.32 mg/kg dose level. Within 24 h of dosing, rats surviving a dose of 1.32 mg/kg exhibited transient decreased body weight and exagg erated AS responding. Startle latency and habituation, PA, and CAR wer e not affected. Examination of brains from six rats per group revealed a subset (2/6) of animals receiving 1.32 mg/kg domoic acid with degen erating neurons in the hippocampal CA1/CA3 subregions and gliosis. The decreased body weight and increased startle suggest a hyperreactivity syndrome possibly related to neuronal degeneration in the hippocampus . In a separate experiment, domoic acid at an IP dose of 0.93 mg/kg wa s found to produce hypomotility in addition to a decrease in body weig ht. Both effects were reduced by pretreatment with scopolamine (2 mg/k g), but not with caffeine (30 mg/kg), indicating a possible cholinergi c involvement in domoate's toxicity. Copyright (C) 1996 Elsevier Scien ce Inc.