Sobotka T J, Brown R, Quander D Y, Jackson R, Smith M, Long S A, Barton C N, Rountree R L, Hall S, Eilers P, Johannessen J N, Scallet A C
Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington, DC 20204, USA.
Neurotoxicol Teratol. 1996 Nov-Dec;18(6):659-70. doi: 10.1016/s0892-0362(96)00120-1.
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.
对成年大鼠腹腔注射0、0.22、0.65或1.32毫克/千克的软骨藻酸，然后测试其被动回避（PA）、听觉惊吓（AS）或条件回避（CAR）行为。仅在1.32毫克/千克剂量水平观察到临床症状。给药后24小时内，存活于1.32毫克/千克剂量的大鼠体重短暂下降，听觉惊吓反应增强。惊吓潜伏期、习惯化、被动回避和条件回避均未受影响。对每组六只大鼠的大脑进行检查发现，接受1.32毫克/千克软骨藻酸的动物中有一部分（2/6）海马CA1/CA3亚区神经元发生退化并出现胶质增生。体重下降和惊吓反应增强表明可能存在一种与海马神经元退化相关的反应亢进综合征。在另一项实验中，发现腹腔注射剂量为0.93毫克/千克的软骨藻酸除了会导致体重下降外，还会引起运动减少。这两种效应都可通过用东莨菪碱（2毫克/千克）预处理而减轻，但用咖啡因（30毫克/千克）预处理则无效，这表明软骨藻酸毒性可能涉及胆碱能机制。
