Walters D E, Chapman C D, Howard S G
Department of Pharmacology, University of California, Los Angeles 90024.
J Neurochem. 1990 Jan;54(1):181-6. doi: 10.1111/j.1471-4159.1990.tb13299.x.
Haloperidol-induced dopamine (DA) release and metabolism were studied in the rat striatum at 10-11, 21-22, and 35-36 days of age using intracerebral dialysis and HPLC with electrochemical detection. There was an age-related increase in basal DA release and extracellular levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), with the greatest increases occurring between 10-11 and 21-22 days of age. Haloperidol (0.1 mg/kg, i.p.) significantly increased DA release at each age compared to control. Also, haloperidol produced a significantly greater increase in DA release at 10-11 days than at 21-22 or 35-36 days of age when expressed as percentage of predrug release. Haloperidol increased DA release over 60 min to 235%, 138%, and 158% above baseline at 10-11, 21-22, and 35-36 days of age, respectively, after which time the levels remained relatively constant. Haloperidol significantly increased extracellular DOPAC and HVA levels at each age compared to controls, but there were no significant differences in DOPAC or HVA levels between ages in response to haloperidol. The results indicate that, at 10 days of age, DA release in the striatum is physiologically functional and that the regulatory feedback control of DA release and metabolism in the striatum develops prior to 10 days of age.
采用脑内透析和高效液相色谱电化学检测法,研究了10 - 11日龄、21 - 22日龄和35 - 36日龄大鼠纹状体中氟哌啶醇诱导的多巴胺(DA)释放及代谢情况。基础DA释放以及3,4 - 二羟基苯乙酸(DOPAC)和高香草酸(HVA)的细胞外水平呈现与年龄相关的增加,其中在10 - 11日龄和21 - 22日龄之间增加最为显著。与对照组相比,氟哌啶醇(0.1mg/kg,腹腔注射)在各年龄组均显著增加了DA释放。此外,以给药前释放量的百分比表示时,氟哌啶醇在10 - 11日龄时引起的DA释放增加显著大于21 - 22日龄或35 - 36日龄。在10 - 11日龄、21 - 22日龄和35 - 36日龄时,氟哌啶醇使DA释放量在60分钟内分别比基线水平高出235%、138%和158%,此后水平保持相对稳定。与对照组相比,氟哌啶醇在各年龄组均显著增加了细胞外DOPAC和HVA水平,但在氟哌啶醇作用下,各年龄组之间DOPAC或HVA水平无显著差异。结果表明,在10日龄时,纹状体中的DA释放具有生理功能,并且纹状体中DA释放和代谢的调节反馈控制在10日龄之前就已发育。