Prus Adam J, Huang Mei, Li Zhu, Dai Jin, Meltzer Herbert Y
Psychology Department, Northern Michigan University, Marquette, MI 49855, USA.
Brain Res. 2007 Dec 12;1184:354-64. doi: 10.1016/j.brainres.2007.09.092. Epub 2007 Oct 12.
NT69L is a novel neurotensin (8-13) analog that produces atypical antipsychotic-like effects in animal models. Because atypical antipsychotic drugs increase dopamine (DA) and acetylcholine (ACh) efflux in the medial prefrontal cortex and DA efflux in the nucleus accumbens, the present study sought to further evaluate the putative antipsychotic-like effects of NT69L by assessing DA and ACh efflux in these regions. Dual probe microdialysis was conducted in awake freely moving male rats, without using an acetylcholinesterase inhibitor in the perfusion medium. NT69L (1.0 and 3.0 mg/kg) produced significant increases in extracellular DA and ACh efflux in the medial prefrontal cortex. NT69L (1.0 mg/kg, but not 3.0 mg/kg) produced a significant increase of DA, but not ACh, efflux in the nucleus accumbens. Pretreatment with the serotonin (5-HT)(1A) receptor antagonist WAY100635 (0.2 mg/kg) significantly attenuated the 3.0 mg/kg NT69L-induced increase in medial prefrontal cortical DA efflux. Pretreatment with NT69L (1.0 mg/kg) significantly potentiated the effects of the atypical antipsychotic drug risperidone (0.1 mg/kg) on DA, but not ACh, efflux in the medial prefrontal cortex, while pretreatment with NT69L 1.0 mg/kg failed to alter the effects of haloperidol (0.1 mg/kg) on DA or ACh efflux in either region. These findings further suggest that NT analogs may be useful alone or adjunctively for the treatment of schizophrenia.
NT69L是一种新型神经降压素(8 - 13)类似物,在动物模型中产生非典型抗精神病样效应。由于非典型抗精神病药物会增加内侧前额叶皮质中的多巴胺(DA)和乙酰胆碱(ACh)外流以及伏隔核中的DA外流,本研究旨在通过评估这些区域中的DA和ACh外流来进一步评估NT69L假定的抗精神病样效应。在清醒自由活动的雄性大鼠中进行双探针微透析,灌注介质中不使用乙酰胆碱酯酶抑制剂。NT69L(1.0和3.0 mg/kg)使内侧前额叶皮质中的细胞外DA和ACh外流显著增加。NT69L(1.0 mg/kg,但不是3.0 mg/kg)使伏隔核中的DA外流显著增加,但ACh外流未增加。用5-羟色胺(5-HT)(1A)受体拮抗剂WAY100635(0.2 mg/kg)预处理可显著减弱3.0 mg/kg NT69L诱导的内侧前额叶皮质DA外流增加。用NT69L(1.0 mg/kg)预处理可显著增强非典型抗精神病药物利培酮(0.1 mg/kg)对内侧前额叶皮质中DA外流的作用,但对ACh外流无作用,而用1.0 mg/kg NT69L预处理未能改变氟哌啶醇(0.1 mg/kg)对任一区域中DA或ACh外流的作用。这些发现进一步表明,NT类似物可能单独或辅助用于治疗精神分裂症。