Trent F, Nakamura S, Tepper J M
Aidekman Research Center, Rutgers, State University of New Jersey, Newark 07102.
Eur J Pharmacol. 1991 Nov 12;204(3):265-72. doi: 10.1016/0014-2999(91)90851-g.
The effects of amphetamine, apomorphine and haloperidol on the spontaneous activity of electrophysiologically identified nigral dopaminergic neurons were examined with extracellular recordings in vivo in neonatal rats ranging in age from postnatal day 1 to postnatal day 28, and in adult rats. In postnatal day 1-6 pups amphetamine (5 mg/kg i.p.) produced a paradoxical increase in neuronal firing in 45% and had no effect on 30% of the 20 neurons examined. During the second week half of the neurons recorded were unresponsive to amphetamine. Typical amphetamine-induced inhibition was observed in only 25% of the neurons from postnatal day 1-6 and 50% of those from postnatal day 7-15 rats compared to 81.8% in postnatal day 16-28 pups and 100% in adults. Apomorphine (50-200 micrograms/kg i.p.; 5-20 micrograms/kg i.v.), significantly inhibited the spontaneous activity of dopaminergic neurons, including cells that previously failed to be inhibited by amphetamine, independent of age. The apomorphine-induced inhibition was consistently reversed by administration of haloperidol (0.5-2.0 mg/kg, i.p.; 50-200 micrograms/kg i.v.). The anomalous responses to amphetamine in early neonatal rats may be related to its paradoxical behavioral effects in human children afflicted with attention deficit disorder.
利用细胞外记录法，在出生后1天至28天的新生大鼠及成年大鼠体内，研究了苯丙胺、阿扑吗啡和氟哌啶醇对经电生理学鉴定的黑质多巴胺能神经元自发活动的影响。在出生后1至6天的幼鼠中，苯丙胺（腹腔注射5mg/kg）使45%的神经元放电出现反常增加，对所检测的20个神经元中的30%没有影响。在第二周，所记录的神经元中有一半对苯丙胺无反应。与出生后16至28天幼鼠中的81.8%以及成年大鼠中的100%相比，在出生后1至6天的幼鼠中只有25%的神经元、出生后7至15天的幼鼠中有50%的神经元出现典型的苯丙胺诱导的抑制作用。阿扑吗啡（腹腔注射50 - 200μg/kg；静脉注射5 - 20μg/kg）显著抑制多巴胺能神经元的自发活动，包括先前未被苯丙胺抑制的细胞，且与年龄无关。给予氟哌啶醇（腹腔注射0.5 - 2.0mg/kg；静脉注射50 - 200μg/kg）可使阿扑吗啡诱导的抑制作用持续逆转。新生大鼠早期对苯丙胺的异常反应可能与其在患有注意力缺陷障碍的人类儿童中的反常行为效应有关。
