Tanda Gianluigi, Valentini Valentina, De Luca Maria Antonietta, Perra Valentina, Serra Gian Pietro, Di Chiara Gaetano
Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy.
Psychopharmacology (Berl). 2015 Apr;232(8):1427-40. doi: 10.1007/s00213-014-3780-2. Epub 2014 Oct 28.
The only systematic in vivo studies comparing antipsychotic (AP) effects on nucleus accumbens (NAc) shell and core dopamine (DA) transmission are voltammetric studies performed in pargyline-pretreated, halothane-anaesthetized rats. Studies in freely moving rats not pretreated with pargyline are not available. This study was intended to fill this gap by the use of in vivo microdialysis in freely moving rats.
Male Sprague-Dawley rats were implanted with microdialysis probes in the NAc shell and core and medial prefrontal cortex (PFCX). The next day, rats were administered intravenously with two or three doses of APs, and dialysate DA was monitored in 10-min samples. Some rats were pretreated with pargyline (75 mg/kg i.p.) and after 1 h were given clozapine or risperidone.
Clozapine, risperidone, quetiapine, raclopride, sulpiride and amisulpride increased DA preferentially in the NAc shell. Such preferential effect on shell DA was not observed after haloperidol, chlorpromazine and olanzapine. In contrast to voltammetric studies, a preferential effect on NAc core DA was not observed after any dose of AP. Pargyline pretreatment did not reduce but actually amplified the preferential effect of clozapine and risperidone on NAc shell DA.
Apart from raclopride and olanzapine, the APs with lower extrapyramidal effects could be distinguished from typical APs on the basis of their ability to preferentially stimulate DA transmission in the NAc shell. There was no relationship between stimulation of PFCX DA and atypical APs profile. The differences between this study and voltammetry studies were not attributable to pargyline pretreatment.
唯一比较抗精神病药物（AP）对伏隔核（NAc）壳部和核心多巴胺（DA）传递影响的系统性体内研究是在使用帕吉林预处理、氟烷麻醉的大鼠身上进行的伏安法研究。目前尚无关于未用帕吉林预处理的自由活动大鼠的研究。本研究旨在通过在自由活动大鼠中使用体内微透析来填补这一空白。
将雄性Sprague-Dawley大鼠在NAc壳部、核心以及内侧前额叶皮质（PFCX）植入微透析探针。次日，给大鼠静脉注射两剂或三剂AP，并在10分钟的样本中监测透析液中的DA。部分大鼠用帕吉林（75mg/kg腹腔注射）预处理，1小时后给予氯氮平或利培酮。
氯氮平、利培酮、喹硫平、雷氯必利、舒必利和氨磺必利优先增加NAc壳部的DA。氟哌啶醇、氯丙嗪和奥氮平给药后未观察到对壳部DA的这种优先作用。与伏安法研究不同，任何剂量的AP给药后均未观察到对NAc核心DA的优先作用。帕吉林预处理并未降低，反而增强了氯氮平和利培酮对NAc壳部DA的优先作用。
除雷氯必利和奥氮平外，锥体外系作用较低的AP可根据其优先刺激NAc壳部DA传递的能力与典型AP区分开来。PFCX DA的刺激与非典型AP特征之间没有关系。本研究与伏安法研究的差异并非归因于帕吉林预处理。
