Modification of the behavioral effects of morphine in rats by serotonin 5-HT₁A and 5-HT₂A receptor agonists: antinociception, drug discrimination, and locomotor activity.
Modification of the behavioral effects of morphine in rats by serotonin 5-HT₁A and 5-HT₂A receptor agonists: antinociception, drug discrimination, and locomotor activity.
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DOI：
10.1007/s00213-012-2870-2
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发表时间：
2013-02
影响因子：
3.4
通讯作者：
France, Charles P.
中科院分区：
文献类型：
--
作者：
Li, Jun-Xu;Shah, Aparna P.;Patel, Sunny K.;Rice, Kenner C.;France, Charles P.
间接作用的血清素（5-HT）受体激动剂可以增强吗啡的镇痛作用；然而，介导这种增强的特定 5-HT 受体亚型尚未确定。本研究通过镇痛（辐射热甩尾和温水缩尾）、药物辨别（3.2 mg/kg 吗啡与生理盐水）和运动等措施，研究了大鼠中吗啡与 5-HT1A 和 5-HT2A 受体激动剂之间的相互作用。雄性 Sprague-Dawley 大鼠（每组 7-8 只）用于检查吗啡单独使用以及与 DOM（5-HT2A 激动剂）和 8-OH-DPAT（5-HT1A 激动剂）联合使用的效果。 DOM 不会改变镇痛或歧视刺激作用，同时适度减弱吗啡的运动刺激作用； DOM (0.32 mg/kg) 对吗啡诱导的运动的影响被 5-HT2A 受体选择性拮抗剂 MDL 100907 阻止。相反，8-OH-DPAT (0.032–0.32 mg/kg) 完全减弱了镇痛作用（两种方法），没有改变辨别刺激作用，并且增强了（0.32 mg/kg）吗啡的运动刺激作用。 5-HT1A 受体选择性拮抗剂 WAY100635 可阻止 8-OH-DPAT 的这些作用。作用于 5-HT1A 或 5-HT2A 受体的激动剂不会以类似的方式改变 mu 阿片受体激动剂的所有作用。此外，5-HT 和阿片受体激动剂之间的相互作用在大鼠和非人灵长类动物之间存在显着差异，这强调了在广泛的条件下和多个物种中比较药物相互作用的价值。
Indirect-acting serotonin (5-HT) receptor agonists can enhance the antinociceptive effects of morphine; however, the specific 5-HT receptor subtype(s) mediating this enhancement is not established. This study examined interactions between morphine and both 5-HT1A and 5-HT2A receptor agonists in rats using measures of antinociception (radiant heat tail flick and warm water tail withdrawal), drug discrimination (3.2 mg/kg morphine versus saline), and locomotion. Male Sprague-Dawley rats (n=7–8 per group) were used to examine the effects of morphine alone and in combination with DOM (5-HT2A agonist) and 8-OH-DPAT (5-HT1A agonist). DOM did not modify antinociceptive or discriminative stimulus effects while modestly attenuating locomotor-stimulating effects of morphine; the effect of DOM (0.32 mg/kg) on morphine-induced locomotion was prevented by the 5-HT2A receptor selective antagonist MDL 100907. In contrast, 8-OH-DPAT (0.032–0.32 mg/kg) fully attenuated the antinociceptive effects (both procedures), did not modify the discriminative stimulus effects, and enhanced (0.32 mg/kg) the locomotor-stimulating effects of morphine. These effects of 8-OH-DPAT were prevented by the 5-HT1A receptor selective antagonist WAY100635. Agonists acting at 5-HT1A or 5-HT2A receptors do not modify all effects of mu opioid receptor agonists in a similar manner. Moreover, interactions between 5-HT and opioid receptor agonists vary significantly between rats and nonhuman primates, underscoring the value of comparing drug interactions across a broad range of conditions and in multiple species.
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影响因子：
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