大鼠和小鼠中5-羟色胺受体亚型之间功能相互作用的行为学证据。
Behavioural evidence for functional interactions between 5-HT-receptor subtypes in rats and mice.
作者信息
Berendsen H H, Broekkamp C L
机构信息
Dept. CNS Pharmacology, Organon International B.V., OSS, The Netherlands.
出版信息
Br J Pharmacol. 1990 Nov;101(3):667-73. doi: 10.1111/j.1476-5381.1990.tb14138.x.
Abstract
- 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-HT2/1C-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 (less than 1 mg kg-1) it potentiated, and at higher doses (greater than 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 10mg kg- '. 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.
摘要
- 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受体的化合物会产生行为效应，这可能是反应竞争或中枢神经系统内不同通路之间特定相互作用的结果。因此，对不同5-HT受体亚型之间的相互作用进行了研究。2. 5-HT1A激动剂8-羟基-二丙基氨基四氢萘（8-OH-DPAT）诱导的小鼠体温过低和活动减少可被选择性5-HT1C激动剂MK 212、1-（间氯苯基）-哌嗪（mCPP）和间三氟甲基苯基哌嗪（TFMPP）以及5-HT2/1C混合激动剂1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷（DOI）减弱。10mg/kg的5-HT1A/1B混合激动剂CGS 12066B增强了体温过低，对活动减少无影响。3. 5-HT1A激动剂8-OH-DPAT诱导的大鼠前爪踩踏可被5-HT1C激动剂MK 212和mCPP减弱。5-HT1C激动剂TFMPP具有双峰效应：低剂量（小于1mg/kg）时增强，高剂量（大于2.2mg/kg）时减弱前爪踩踏，5-HT2/1C混合激动剂DOI产生5-HT2相关行为并增强8-OH-DPAT诱导的前爪踩踏。这表明5-HT1C受体激活具有减弱作用，5-HT2受体激活具有增强作用。CGS 12066B在这方面无作用。4. DOI诱导的大鼠头部抖动可被8-OH-DPAT、TFMPP、mCPP和MK 212减弱。半数抑制剂量分别为0.03、0.7、0.1和0.2mg/kg。这表明5-HT2受体介导的效应可能被5-HT1A或5-HT1C受体的激活减弱。CGS 12066B减弱了头部抖动反应，但仅在10mg/kg时有效。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5-HT受体亚型具有或多或少相等的亲和力时，在从功能测量得出结论时需要谨慎。
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