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 conditioned 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 exaggerated AS responding. Startle latency and habituation, PA, and CAR were 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 degenerating 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 was found to produce hypomotility in addition to a decrease in body weight. Both effects were reduced by pretreatment with scopolamine (2 mg/kg), but not with caffeine (30 mg/kg), indicating a possible cholinergic involvement in domoate's toxicity.
AuthorsT J Sobotka, R Brown, D Y Quander, R Jackson, M Smith, S A Long, C N Barton, R L Rountree, S Hall, P Eilers, J N Johannessen, A C Scallet
JournalNeurotoxicology and teratology (Neurotoxicol Teratol) 1996 Nov-Dec Vol. 18 Issue 6 Pg. 659-70 ISSN: 0892-0362 [Print] UNITED STATES
PMID8947943 (Publication Type: Journal Article)
Chemical References
  • Neurotoxins
  • domoic acid
  • Kainic Acid
  • Acoustic Stimulation
  • Analysis of Variance
  • Animals
  • Astrocytes (drug effects, pathology)
  • Avoidance Learning (drug effects)
  • Body Weight
  • Conditioning, Operant
  • Dose-Response Relationship, Drug
  • Habituation, Psychophysiologic
  • Hippocampus (drug effects, pathology)
  • Injections, Intraperitoneal
  • Kainic Acid (analogs & derivatives, toxicity)
  • Male
  • Neurotoxins (toxicity)
  • Rats
  • Rats, Sprague-Dawley
  • Reflex, Startle (drug effects)

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