Abstract：
OBJECTIVE: For understanding the neurochemical mechanism of neuropsychiatric conditions associated with cognitive deficits it is of major relevance to elucidate the influence of serotonin (5-HT) agonists and antagonists on memory function as well dopamine (DA) and 5-HT release and metabolism. In the present study, we assessed the effects of the 5-HT2A receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) and the 5-HT2A receptor altanserin (ALT) on object and place recognition memory and cerebral neurotransmitters and metabolites in the rat.
METHODS: Rats underwent a 5-min exploration trial in an open field with two identical objects. After systemic injection of a single dose of either DOI (0.1 mg/kg), ALT (1 mg/kg) or the respectice vehicle (0.9 % NaCl, 50 % DMSO), rats underwent a 5-min test trial with one of the objects replaced by a novel one and the other object transferred to a novel place. Upon the assessment of object exploration and motor/exploratory behaviors, rats were sacrificed. DA, 5-HT and metabolite levels were analyzed in cingulate (CING), caudateputamen (CP), nucleus accumbens (NAC), thalamus (THAL), dorsal (dHIPP) and ventral hippocampus (vHIPP), brainstem and cerebellum with high performance liquid chromatography.
RESULTS: DOI decreased rearing but increased head-shoulder motility relative to vehicle. Memory for object and place after both DOI and ALT was not different from vehicle. Network analyses indicated that DOI inhibited DA metabolization in CING, CP, NAC, and THAL, but facilitated it in dHIPP. Likewise, DOI inhibited 5-HT metabolization in CING, NAC, and THAL. ALT facilitated DA metabolization in the CING, NAC, dHIPP, vHIPP, and CER, but inhibited it in the THAL. Additionally, ALT facilitated 5-HT metabolization in NAC and dHIPP.
CONCLUSIONS: DOI and ALT differentially altered the quantitative relations between the neurotransmitter/metabolite levels in the individual brain regions, by inducing region-specific shifts in the metabolization pathways. Findings are relevant for understanding the neurochemistry underlying DAergic and/or 5-HTergic dysfunction in neurological and psychiatric conditions.
METHODS: Rats underwent a 5-min exploration trial in an open field with two identical objects. After systemic injection of a single dose of either DOI (0.1 mg/kg), ALT (1 mg/kg) or the respectice vehicle (0.9 % NaCl, 50 % DMSO), rats underwent a 5-min test trial with one of the objects replaced by a novel one and the other object transferred to a novel place. Upon the assessment of object exploration and motor/exploratory behaviors, rats were sacrificed. DA, 5-HT and metabolite levels were analyzed in cingulate (CING), caudateputamen (CP), nucleus accumbens (NAC), thalamus (THAL), dorsal (dHIPP) and ventral hippocampus (vHIPP), brainstem and cerebellum with high performance liquid chromatography.
RESULTS: DOI decreased rearing but increased head-shoulder motility relative to vehicle. Memory for object and place after both DOI and ALT was not different from vehicle. Network analyses indicated that DOI inhibited DA metabolization in CING, CP, NAC, and THAL, but facilitated it in dHIPP. Likewise, DOI inhibited 5-HT metabolization in CING, NAC, and THAL. ALT facilitated DA metabolization in the CING, NAC, dHIPP, vHIPP, and CER, but inhibited it in the THAL. Additionally, ALT facilitated 5-HT metabolization in NAC and dHIPP.
CONCLUSIONS: DOI and ALT differentially altered the quantitative relations between the neurotransmitter/metabolite levels in the individual brain regions, by inducing region-specific shifts in the metabolization pathways. Findings are relevant for understanding the neurochemistry underlying DAergic and/or 5-HTergic dysfunction in neurological and psychiatric conditions.
摘要：
目的：为了了解与认知缺陷相关的神经精神病症的神经化学机制，阐明5-羟色胺（5-HT）激动剂和拮抗剂对记忆功能以及多巴胺（DA）和5-HT释放和代谢的影响具有重要意义。出于这个原因,我们评估了2,5-二甲氧基-4-碘苯丙胺(DOI)和altanserin(ALT)对大鼠物位识别记忆、脑神经递质和代谢产物的影响.
方法：大鼠在具有两个相同物体的空地中进行了5分钟的探索试验。全身注射单剂量DOI（0.1mg/kg）后，ALT（1mg/kg）或相应载体（0.9%NaCl，50%DMSO),大鼠进行了5分钟的测试试验，其中一个物体被一个新的物体代替，另一个物体转移到一个新的地方。在评估对象探索和运动/探索行为时，处死大鼠。DA,分析扣带回(CING)中的5-HT和代谢物水平，caudateputamen（CP），伏隔核（NAC），丘脑(THAL),背侧（dHIPP）和腹侧海马（vHIPP），脑干和小脑高效液相色谱法。
结果：DOI相对于载体降低了饲养，但增加了头肩运动。DOI和ALT后的对象和位置的内存与车辆没有区别。网络分析表明DOI抑制了CING中的DA代谢，CP,NAC,和THAL,但在dHIPP中促进了它。同样，DOI抑制CING中的5-HT代谢，NAC,和THAL。ALT促进CING中的DA代谢，NAC,dHIPP,vHIPP,和CER,但抑制了它在THAL。此外,ALT促进NAC和dHIPP中的5-HT代谢。
结论：DOI和ALT差异改变了单个脑区神经递质/代谢物水平之间的定量关系，通过诱导代谢途径的区域特异性变化。研究结果与了解神经和精神疾病中DAerc能和/或5-HTerc能功能障碍的神经化学相关。
方法：大鼠在具有两个相同物体的空地中进行了5分钟的探索试验。全身注射单剂量DOI（0.1mg/kg）后，ALT（1mg/kg）或相应载体（0.9%NaCl，50%DMSO),大鼠进行了5分钟的测试试验，其中一个物体被一个新的物体代替，另一个物体转移到一个新的地方。在评估对象探索和运动/探索行为时，处死大鼠。DA,分析扣带回(CING)中的5-HT和代谢物水平，caudateputamen（CP），伏隔核（NAC），丘脑(THAL),背侧（dHIPP）和腹侧海马（vHIPP），脑干和小脑高效液相色谱法。
结果：DOI相对于载体降低了饲养，但增加了头肩运动。DOI和ALT后的对象和位置的内存与车辆没有区别。网络分析表明DOI抑制了CING中的DA代谢，CP,NAC,和THAL,但在dHIPP中促进了它。同样，DOI抑制CING中的5-HT代谢，NAC,和THAL。ALT促进CING中的DA代谢，NAC,dHIPP,vHIPP,和CER,但抑制了它在THAL。此外,ALT促进NAC和dHIPP中的5-HT代谢。
结论：DOI和ALT差异改变了单个脑区神经递质/代谢物水平之间的定量关系，通过诱导代谢途径的区域特异性变化。研究结果与了解神经和精神疾病中DAerc能和/或5-HTerc能功能障碍的神经化学相关。
