Levine T E, Erinoff L, Dregits D P, Seiden L S
Pharmacol Biochem Behav. 1980 Feb;12(2):281-5. doi: 10.1016/0091-3057(80)90369-x.
Rats were given intraventricular injections of 6-hydroxydopamine (6-HDA) or saline-ascorbate vehicle as neonates (3-days old) and as adults (49 and 51 days old). At 73 days of age, they were trained on a random interval 90-sec schedule of water reinforcement. The rats treated with 6-HDA as adults stabilized at response rates approximately twice those of vehicle-treated rats, while rats treated with 6-HDA as neonates showed response rates which were not significantly different from vehicle-treated rats; Both L-Dopa and apomorphine decreased response rates at all doses tested. There were no differences among the groups with respect to the effect of these drugs. Adult-treated rats showed greater response rate decreases following peripheral decarboxylase inhibition with Ro 4-4602. Catecholamine analyses revealed the rats treated with 6-HDA as neonates had greater depletions in the striatum and the remainder of telencephalon than adult-treated rats but an increase in brainstem norepinephrine. These findings suggest that age of treatment is an important determinant of the biochemical and behavioral effects of treatment with 6-HDA.
给新生大鼠(3日龄)和成年大鼠(49和51日龄)脑室内注射6-羟基多巴胺(6-HDA)或生理盐水-抗坏血酸载体。在73日龄时,对它们进行随机间隔90秒的水强化训练。成年期接受6-HDA治疗的大鼠稳定在大约是接受载体治疗大鼠反应率两倍的水平,而新生期接受6-HDA治疗的大鼠的反应率与接受载体治疗的大鼠无显著差异;左旋多巴和阿扑吗啡在所有测试剂量下均降低了反应率。在这些药物的作用方面,各实验组之间没有差异。成年期接受治疗的大鼠在使用Ro 4-4602抑制外周脱羧酶后反应率下降幅度更大。儿茶酚胺分析显示,新生期接受6-HDA治疗的大鼠纹状体和端脑其余部分的耗竭程度比成年期接受治疗的大鼠更大,但脑干去甲肾上腺素有所增加。这些发现表明,治疗年龄是6-HDA治疗的生化和行为效应的重要决定因素。