See R E, Lynch A M, Aravagiri M, Nemeroff C B, Owens M J
Department of Psychology, Washington State University, Pullman 99164-4820, USA.
Brain Res. 1995 Dec 18;704(2):202-9. doi: 10.1016/0006-8993(95)01114-5.
Chronic neuroleptic administration has previously been shown to alter in vivo measures of dopaminergic function and lead to regionally selective increases in neurotensin levels. In the current study, female rats were administered chronic haloperidol for 6 months via subcutaneous silastic implants. After 24 weeks of administration, microdialysis probes were inserted into the lateral caudate putamen and the medial prefrontal cortex. Basal samples were collected prior to infusion of a high K+ concentration (100 mM KCl). Extracellular concentrations of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid were assessed using HPLC. Chronic haloperidol-treated rats showed increased basal dopamine metabolite levels in the caudate putamen and an altered response to the effects of high K+ on 3,4-dihydroxyphenylacetic acid; no significant differences were seen with other analytes in the caudate putamen. Although basal concentrations were not different between groups in the prefrontal cortex, haloperidol-treated rats showed a significant attenuation of response to the effects of high K+ infusion on dopamine metabolite concentrations. Radioimmunoassay measurement of tissue neurotensin content showed highly significant elevations of neurotensin concentrations in the caudate putamen and nucleus accumbens, but not in other brain regions analyzed. These results suggest a confluence of altered dopamine and neurotensin function in the caudate putamen which may be related to motor side effects of haloperidol, whereas changes in prefrontal dopamine function are not associated with altered neurotensin levels.
先前的研究表明，长期服用抗精神病药物会改变体内多巴胺能功能的指标，并导致神经降压素水平出现区域选择性升高。在本研究中，通过皮下硅橡胶植入物对雌性大鼠进行为期6个月的氟哌啶醇慢性给药。给药24周后，将微透析探针插入尾状核壳外侧和内侧前额叶皮质。在注入高钾浓度（100 mM KCl）之前收集基础样本。使用高效液相色谱法评估多巴胺、3,4-二羟基苯乙酸、高香草酸和5-羟吲哚乙酸的细胞外浓度。慢性氟哌啶醇治疗的大鼠尾状核壳中的基础多巴胺代谢物水平升高，并且对高钾对3,4-二羟基苯乙酸的影响的反应发生改变；尾状核壳中的其他分析物未观察到显著差异。虽然前额叶皮质组间的基础浓度没有差异，但氟哌啶醇治疗的大鼠对高钾注入对多巴胺代谢物浓度的影响的反应显著减弱。组织神经降压素含量的放射免疫测定显示，尾状核壳和伏隔核中的神经降压素浓度显著升高，但在分析的其他脑区中未升高。这些结果表明，尾状核壳中多巴胺和神经降压素功能的改变可能与氟哌啶醇的运动副作用有关，而前额叶多巴胺功能的变化与神经降压素水平的改变无关。
