BEHAVIORAL EVIDENCE FOR FUNCTIONAL INTERACTIONS BETWEEN 5-HT-RECEPTOR SUBTYPES IN RATS AND MICE
BEHAVIORAL EVIDENCE FOR FUNCTIONAL INTERACTIONS BETWEEN 5-HT-RECEPTOR SUBTYPES IN RATS AND MICE
复制标题
DOI：
10.1111/j.1476-5381.1990.tb14138.x
复制
发表时间：
1990-11-01
影响因子：
7.3
通讯作者：
BROEKKAMP, CLE
中科院分区：
文献类型：
--
作者：
BERENDSEN, HHG;BROEKKAMP, CLE
1不同的5-羟色胺（5-HT）受体亚型介导不同的行为反应。作用于一种以上5-HT受体的化合物产生行为效应，这可能是反应竞争或CNS内途径之间特异性相互作用的结果。因此，研究了不同5-HT受体亚型之间的相互作用。2,5-HT_（1A）激动剂8-羟基-二丙氨基四氢萘（8-OH-DPAT）引起的小鼠体温降低和活动减少可被5-HT_（1C）激动剂MK 212、间氯苯基哌嗪（mCPP）和间三氟甲基苯基哌嗪（TFMPP）以及5-HT_（2/C）混合激动剂1-（2，5-二甲氧基-4-碘苯基）-2-氨基丙烷（DOI）所减轻。混合5-HT 1A/1B-激动剂CGS 12066 B在10 mg kg-1时可增强体温降低，但对活动减退无影响。35-HT_（1A）激动剂8-OH-DPAT诱导的大鼠前足踩踏反应可被5-HT_（1C）激动剂MK_（212）和mCPP所减弱。5-HT 1C激动剂TFMPP具有双峰效应：在低剂量（< 1 mg kg-1）时，它增强，在高剂量（> 2.2 mg kg-1）时，它减弱前爪踩踏。混合的5-HT 2/1C-激动剂DOI产生5-HT 2-相关行为并增强8-OH-DPAT-诱导的前爪踩踏。这表明5-HT 1C-受体活化的减弱作用和5-HT 2-受体活化的增强作用。CGS 12066 B在这方面没有效果。4. 8-OH-DPAT、TFMPP、mCPP和MK 212对DOI诱导的大鼠头部震颤有明显的抑制作用。ID 50分别为0.03、0.7、0.1和2 mg kg-1。这表明5-HT 2受体介导的作用可通过激活5-HT 1A或5-HT 1C受体而减弱。CGS 12066 B减弱了摇头反应，但仅在10 mg kg-1时。5结果表明，不同5-HT受体亚型介导的事件之间存在相互作用。因此，当化合物对一种以上的5-HT受体亚型具有或多或少相等的亲和力时，从功能测量中得出结论时需要小心。
1 Different 5-hydroxytryptamine (5-HT) receptor subtypes mediate different behavioural responses. Compounds acting at more than one 5-HT receptor exert behavioural effects which may be the result of response competition or a specific interaction between pathways within the CNS. Therefore the mutual interaction between different 5-HT receptor subtypes was studied. 2 Hypothermia and hypoactivity in mice induced by the 5-HT1A-agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) could be attenuated by the preferential 5-HT1C-agonists MK 212, 1-(meta-chlorophenyl)-piperazine (mCPP) and m-trifluoromethyl phenyl piperazine (TFMPP), and by the mixed 5-HT2/C-agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). The mixed 5-HT1A/1B-agonist CGS 12066B at 10 mg kg-1 potentiated hypothermia and had no effect on hypoactivity. 3 Forepaw treading in rats induced by the 5-HT1A-agonist 8-OH-DPAT was attenuated by the 5-HT1C-agonists MK 212 and mCPP. The 5-HT1C-agonist TFMPP had a bimodal effect: at low doses (< 1 mg kg-1) it potentiated, and at higher doses (> 2.2 mg kg-1) it attenuated forepaw treading. the mixed 5-HT2/1C-agonist DOI produced 5-HT2-related behaviours and potentiated 8-OH-DPAT-induced forepaw treading. This indicates an attenuating effect of 5-HT1C-receptor activation and a potentiating effect of 5-HT2-receptor activation. CGS 12066B had no effect in this respect. 4 Head shakes in rats induced by DOI could be attenuated by 8-OH-DPAT, TFMPP, mCPP and MK 212. The ID50s were 0.03, 0.7, 0.1 and 2 mg kg-1, respectively. This suggests that a 5-HT2-receptor-mediated effect may be attenuated by activation of 5-HT1A- or 5-HT1C-receptors. CGS 12066B attenuated the head shake response but only at 10 mg kg-1. 5 The results suggest that interactions exist between the different 5-HT receptor subtype-mediated events. Therefore, care is needed in drawing conclusions from functional measurements when compounds have more or less equal affinities for more than one 5-HT-receptor subtype.