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利用大鼠餐后饱腹感序列对5-HT1B、5-HT1C和5-HT2受体激动剂诱导的食欲减退的行为特异性进行研究。

An examination of the behavioural specificity of hypophagia induced by 5-HT1B, 5-HT1C and 5-HT2 receptor agonists using the post-prandial satiety sequence in rats.

作者信息

Kitchener S J, Dourish C T

机构信息

Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.

出版信息

Psychopharmacology (Berl). 1994 Jan;113(3-4):369-77. doi: 10.1007/BF02245211.

Abstract

Previous studies have shown that administration of 5-HT1B, 5-HT1C or 5-HT2 agonists decreases food intake in rats. However, it has not been established whether these drugs induce satiety or decrease feeding by a non-specific mechanism. In the present study the post-prandial satiety sequence was used to characterise the actions of the 5-HT2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), the 5-HT1B/5-HT1C receptor agonists, 1-(3-chorophenyl) piperazine (mCPP) and 1-[3-(trifluoromethyl)phenyl] piperazine (TFMPP), and the 5-HT1B agonist, 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)H-indole (RU 24969), on feeding in rats. All four compounds reduced food intake in rats that had been food deprived overnight. The 5-HT1B/5-HT1C agonists, TFMPP (at a dose of 1.0 mg/kg) and mCPP (at a dose of 3.0 mg/kg), appeared to produce satiety as their effects on the satiety sequence were similar to those induced by a food pre-load. In contrast, the 5-HT1B agonist RU 24969 and the 5-HT2 agonist DOI did not produce behavioural profiles that resembled satiety. Thus, RU 24969 elevated active behaviours and did not accelerate resting whereas DOI appeared to induce hypophagia by a non-specific fragmentation of behaviour. The results suggest that simultaneous activation of 5-HT1B and 5-HT1C receptors may be sufficient to elicit behaviourally specific satiety in the rat. In contrast, selective activation of 5-HT2 receptors does not induce satiety but elicits active behaviours and decreases feeding by response competition.

摘要

先前的研究表明,给予5-羟色胺1B(5-HT1B)、5-羟色胺1C(5-HT1C)或5-羟色胺2(5-HT2)激动剂可减少大鼠的食物摄入量。然而,这些药物是通过诱导饱腹感还是通过非特异性机制减少进食尚未确定。在本研究中,采用餐后饱腹感序列来表征5-HT2受体激动剂1-(2,5-二甲氧基-4-碘苯基)-2-氨基丙烷(DOI)、5-HT1B/5-HT1C受体激动剂1-(3-氯苯基)哌嗪(mCPP)和1-[3-(三氟甲基)苯基]哌嗪(TFMPP)以及5-HT1B激动剂5-甲氧基-3-(1,2,3,6-四氢-4-吡啶基)H-吲哚(RU 24969)对大鼠进食的影响。所有这四种化合物均减少了禁食过夜大鼠的食物摄入量。5-HT1B/5-HT1C激动剂TFMPP(剂量为1.0毫克/千克)和mCPP(剂量为3.0毫克/千克)似乎产生了饱腹感,因为它们对饱腹感序列的影响与食物预负荷诱导的影响相似。相比之下,5-HT1B激动剂RU 24969和5-HT2激动剂DOI并未产生类似于饱腹感的行为特征。因此,RU 24969增加了活跃行为且未加速静息状态,而DOI似乎通过行为的非特异性碎片化诱导摄食减少。结果表明,同时激活5-HT1B和5-HT1C受体可能足以在大鼠中引发行为特异性饱腹感。相比之下,选择性激活5-HT2受体不会诱导饱腹感,而是引发活跃行为并通过反应竞争减少进食。

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