Behavioral effects of mid-pregnancy administration of lidocaine and mepivacaine in the rat.

R F Smith, G G Wharton, S L Kurtz, K M Mattran, A R Hollenbeck
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Abstract

Sperm-positive female Long-Evans hooded rats were injected with 6 mg/kg lidocaine (with epinephrine), 6 mg/kg mepivacaine, or saline, into the masseter muscle of the jaw on Day 11 of gestation. Birth, growth, and litter composition were unaffected by the drug treatment, as was shuttle box acquisition. Offspring of drug-treated dams had longer latencies than controls on the first day of negative geotaxis training, and were more sensitive to electric footshock. Lidocaine-dosed offspring responded less in the presence of the correct cue in the visual discrimination task, and mepivacaine-dosed animals were hypoactive in the open field. In a second study, offspring of lidocaine-dosed dams were slower to develop the righting reflex, made more errors in acquiring a water maze, had longer suppression times in a conditioned suppression task, and had longer latencies in the tail flick test. Dosing had no effect upon birth and growth, shuttle box, or footshock sensitivity. These data demonstrate that midgestational exposure to lidocaine or mepivacaine at a dose near the limits of permissible human exposure produces significant behavioral changes in the offspring. This preliminary study suggests that development of some portion of the central nervous system is altered by such exposure. Further work is required to determine the parameters and the extent of the effect.

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妊娠中期给予利多卡因和甲哌卡因对大鼠行为的影响。
在妊娠第11天,将精子阳性的雌性龙-埃文斯大鼠下颚咬肌分别注射6 mg/kg利多卡因(含肾上腺素)、6 mg/kg甲哌卡因或生理盐水。药物治疗对出生、生长和产仔组成没有影响,对梭箱的获得也没有影响。药物处理坝的后代在负地向性训练的第一天比对照组有更长的潜伏期,并且对电脚电击更敏感。利多卡因剂量的后代在视觉识别任务中对正确提示的反应较差,而甲哌卡因剂量的后代在开阔场地的活动较低。在第二项研究中,利多卡因小鼠后代的扶正反射发育较慢,在获得水迷宫时出错较多,在条件抑制任务中抑制时间较长,在甩尾测试中潜伏期较长。剂量对出生和生长、穿梭箱或足震敏感性没有影响。这些数据表明,妊娠中期暴露于利多卡因或甲哌卡因,其剂量接近人类允许的暴露限度,会对后代产生显著的行为改变。这项初步研究表明,中枢神经系统的某些部分的发育被这种暴露所改变。需要进一步的工作来确定参数和影响的程度。
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