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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Effect of 5-HT(1B) receptor ligands on self-administration of ethanol in an operant procedure in rats.
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Effect of 5-HT(1B) receptor ligands on self-administration of ethanol in an operant procedure in rats.

机译：5-HT（1B）受体配体对大鼠自我操作中乙醇自我给药的影响。

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摘要

Recent evidence suggests that 5-HT(1B) receptor activation modifies ethanol's reinforcing, intoxicating and discriminative stimulus effects. The present study further explored the role played by 5-HT(1A/1B) receptors by examining their influence on oral ethanol self-administration. Male Wistar rats were trained on an FR 4 schedule to obtain a reinforcer of 0.1 12% w/v ethanol solution. Once responding was stable, the effect of the 5-HT(1A/1B) agonist RU24969 alone and in combination with the 5-HT(1B) antagonist GR127935 or the 5-HT(1A) antagonists (+) WAY100135 and (+) WAY100635 was assessed. The effect of RU24969 on ethanol's pharmacokinetic profile and on operant oral saline self-administration was also examined to assess if alterations in oral ethanol self-administration were due to nonspecific effects on level pressing. For comparison, we examined the effect of another 5-HT(1A/1B) agonist, CGS12066B, on oral ethanol self-administration. Both RU24969 (0.1 to 1 mg/kg) and CGS12066B (0.1 to 1 mg/kg) significantly suppressed oral ethanol self-administration. Administration of GR127935 (1 mg/kg), significantly reversed the effects elicited by RU24969, whereas neither WAY100635 (1 mg/kg) nor (+)WAY100135 (1 mg/kg) had any effect. The effects of lower doses of RU24969 on oral ethanol self-administration were selective as oral saline self-administration and blood ethanol levels were not altered by these doses. These data demonstrate that 5-HT(1B) receptor activation suppresses oral ethanol self-administration. These studies provide further evidence that 5-HT(1B) receptors play a modulatory role in ethanol's behavioral effects.
机译：最近的证据表明，5-HT（1B）受体激活可以改变乙醇的增强，醉人和歧视性刺激效果。本研究通过检查5-HT（1A / 1B）受体对口服乙醇自我给药的影响，进一步探讨了它们的作用。以FR 4时间表训练雄性Wistar大鼠以获得0.1 12％w / v乙醇溶液的增强剂。一旦反应稳定，即可单独使用5-HT（1A / 1B）激动剂RU24969，并与5-HT（1B）拮抗剂GR127935或5-HT（1A）拮抗剂（+）WAY100135和（+）结合使用评估WAY100635。还检查了RU24969对乙醇的药代动力学特征和对口服口服生理盐水自我给药的影响，以评估口服乙醇自我给药的变化是否是由于对压力水平的非特异性影响所致。为了进行比较，我们检查了另一种5-HT（1A / 1B）激动剂CGS12066B对口服乙醇自我给药的作用。 RU24969（0.1至1 mg / kg）和CGS12066B（0.1至1 mg / kg）均显着抑制了口服乙醇的自我给药。 GR127935（1 mg / kg）的施用显着逆转了RU24969引起的作用，而WAY100635（1 mg / kg）和（+）WAY100135（1 mg / kg）均无作用。较低剂量的RU24969对口服乙醇自我给药的影响是选择性的，因为口服生理盐水自我给药且这些剂量不会改变血液乙醇水平。这些数据表明5-HT（1B）受体激活抑制口服乙醇的自我给药。这些研究提供了进一步的证据，表明5-HT（1B）受体在乙醇的行为效应中起调节作用。

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