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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Behaviorally active doses of the CB(1) receptor antagonist SR 141716A increase brain serotonin and dopamine levels and turnover.
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Behaviorally active doses of the CB(1) receptor antagonist SR 141716A increase brain serotonin and dopamine levels and turnover.

机译：CB（1）受体拮抗剂SR 141716A的行为有效剂量可增加脑5-羟色胺和多巴胺的水平和周转率。

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摘要

Large doses (10-40 mg/kg) of the selective cannabinoid CB(1) receptor antagonist, SR 141716A, produce the head-twitch response (HTR) and scratching in rodents and vomiting in the least shrew (Cryptotis parva). Agents that increase brain serotonin (5-HT) levels induce the HTR in rodents, whereas enhancements in either brain 5-HT or dopamine concentrations can lead to production of emesis in vomiting species. The present study was undertaken to demonstrate whether large doses of SR 141716A can (1) induce the HTR and scratching in the least shrew and (2) cause concurrent biochemical changes in brain 5-HT and dopamine concentrations. SR 141716A (0, 1, 5, 10, 20 and 40 mg/kg ip) administration induced the HTR, scratching and vomiting. The HTR effect was bell shaped with a maximum frequency occurring at the 20 mg/kg SR 141716A dose, whereas the scratching and vomiting behaviors displayed dose-dependent effects. The selective 5-HT(2A/C) receptor antagonist, SR 46349B (0, 0.1, 0.25, 1, 3 and 6 mg/kg ip), differentially attenuated all SR 141716A (20 mg/kg)-induced behaviors because the HTR was relatively more potently and completely blocked. In the shrew forebrain, SR 141716A (20 and 40 mg/kg ip) caused dose- and time-dependent increases in the levels of 5-HT and dopamine and the concentrations of their major metabolites [5-hydroxyindole acetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA)] and the turnover of both monoamines. Although the effects of SR 141716A on brainstem concentrations of both monoamines and their metabolites were not always consistent, the CB(1) antagonist did increase the turnover of both 5-HT and dopamine. The present findings suggest that the mechanism and the neurochemical substrate for SR 141716A-induced HTR and scratching behaviors is enhancement of 5-HT release, whereas increased release of 5-HT and dopamine probably contributes to the production of emesis.
机译：大剂量（10-40 mg / kg）的选择性大麻素CB（1）受体拮抗剂SR 141716A会在啮齿类动物中产生头抽搐反应（HTR）并抓挠，并以最少的sh（Cryptotis parva）呕吐。增加大脑5-羟色胺（5-HT）水平的物质在啮齿动物中诱导了HTR，而大脑5-HT或多巴胺浓度的增加会导致呕吐物中呕吐的产生。进行本研究以证明大剂量的SR 141716A是否可以（1）在最少的sh中诱导HTR和刮擦，并且（2）引起大脑5-HT和多巴胺浓度的同时生化变化。 SR 141716A（0、1、5、10、20和40 mg / kg ip给药）诱导HTR，and抓和呕吐。 HTR效应呈钟形，最大频率出现在20 mg / kg SR 141716A剂量下，而the抓和呕吐行为表现出剂量依赖性。选择性5-HT（2A / C）受体拮抗剂SR 46349B（0、0.1、0.25、1、3和6 mg / kg ip），差异性地减弱了所有SR 141716A（20 mg / kg）诱导的行为，因为HTR被更有效地完全封锁了。在sh前脑中，SR 141716A（20和40 mg / kg ip）引起5-HT和多巴胺水平及其主要代谢物[5-羟吲哚乙酸（5-HIAA）的浓度和时间依赖性增加），3,4-二羟基苯基乙酸（DOPAC）和高香草酸（HVA）]以及两种单胺的周转率。尽管SR 141716A对单胺及其代谢产物的脑干浓度的影响并不总是一致的，但CB（1）拮抗剂确实增加了5-HT和多巴胺的周转率。目前的发现表明，SR 141716A诱导的HTR和抓挠行为的机制和神经化学底物是5-HT释放的增强，而5-HT和多巴胺释放的增加可能有助于呕吐的产生。

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