Kinkead B, Owens M J, Nemeroff C B
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Synapse. 1995 Jul;20(3):244-8. doi: 10.1002/syn.890200308.
It has been well documented that treatment with haloperidol and other typical antipsychotic drugs increase neurotensin (NT) concentrations in the nucleus accumbens and caudate nucleus in adult rats. The NT neuronal system has been found to undergo distinct age-related changes in the rat brain, and therefore, it is of interest to examine the ontogeny of the effects of antipsychotic drug treatment on NT concentrations. In order to determine when, or if, antipsychotic drug treatment has an effect on NT-containing neurons in the developing rat, rat pups received a single dose of haloperidol (2.0 mg/kg, s.c.) or vehicle at 9,14, or 20 days after birth. Regional brain NT concentrations were then measured using a sensitive and specific radioimmunoassay. Treatment with haloperidol had no effect on NT concentrations in any brain region in 10-day-old rat pups. At 15 days of age, haloperidol significantly increased NT concentrations in the caudate nucleus (120% of control, P < 0.05). At 21 days of age, haloperidol increased NT concentrations in the caudate nucleus (193% of control, P < 0.001) and nucleus accumbens (126% of control, P < 0.005) similar to that seen in adult animals. There were no statistically significant gender-related differences found in any age or treatment group studied. These findings indicate that there is a specific time point during post-natal development when rat brain NT systems become responsive to antipsychotic drug administration.
有充分的文献记载，用氟哌啶醇和其他典型抗精神病药物治疗可提高成年大鼠伏隔核和尾状核中的神经降压素（NT）浓度。已发现NT神经元系统在大鼠大脑中会经历明显的年龄相关变化，因此，研究抗精神病药物治疗对NT浓度影响的个体发生情况很有意义。为了确定抗精神病药物治疗在发育中的大鼠中何时（或是否）对含NT的神经元有影响，新生大鼠幼崽在出生后9、14或20天接受单次剂量的氟哌啶醇（2.0mg/kg，皮下注射）或赋形剂。然后使用灵敏且特异的放射免疫分析法测量脑区NT浓度。氟哌啶醇治疗对10日龄大鼠幼崽的任何脑区NT浓度均无影响。在15日龄时，氟哌啶醇显著提高了尾状核中的NT浓度（为对照组的120%，P<0.05）。在21日龄时，氟哌啶醇提高了尾状核（为对照组的193%，P<0.001）和伏隔核（为对照组的126%，P<0.005）中的NT浓度，这与成年动物中观察到的情况相似。在所研究的任何年龄或治疗组中均未发现统计学上显著的性别相关差异。这些发现表明，在出生后发育过程中有一个特定的时间点，此时大鼠脑NT系统对抗精神病药物给药产生反应。
