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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Cannabinoids of diverse structure inhibit two DOI-induced 5-HT(2A) receptor-mediated behaviors in mice.
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Cannabinoids of diverse structure inhibit two DOI-induced 5-HT(2A) receptor-mediated behaviors in mice.

机译：不同结构的大麻素抑制小鼠中两种DOI诱导的5-HT（2A）受体介导的行为。

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We have recently shown that the selective cannabinoid CB(1) receptor antagonist SR 141716A produces robust frequencies of head-twitch response (HTR) and ear-scratch response (ESR) in drug-naive mice. Both behaviors were potently blocked by the selective 5-HT(2A/C) receptor antagonist SR 46349B. Selective 5-HT(2A/C) agonists such as DOI also produce these behaviors in mice. The purpose of the present study was to: (1) investigate whether Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and its analogs [Delta(8)-tetrahydrocannabinol (Delta(8)-THC), HU-210, CP 55,940, and WIN 55,212-2] can prevent the DOI-induced behaviors and (2) to see whether any correlation exists in the ID(50) potency order of these cannabinoids in inhibiting the DOI-induced HTR and ESR relative to their published ED(50) potency profiles in producing the tetrad of behaviors in mice. Thus, at 0 min, different groups of mice were injected intraperitoneally with either vehicle or varying doses of the following cannabinoids: Delta(9)-THC (0.25-20 mg/kg), Delta(8)-THC (2.5-20 mg/kg), HU-210 (0.02-0.5 mg/kg), CP 55,940 (0.004-0.5 mg/kg), and WIN 55,212-2 (0.5-10 mg/kg). Twenty minutes later, each mouse received an intraperitoneal injection of DOI (1 mg/kg) and the frequencies of DOI-induced behaviors (mean +/- S.E.M.) were recorded for the next 20 min. The tested cannabinoids reduced the frequencies of both DOI-induced HTR and ESR in a dose-dependent fashion. HU-210 was the most potent inhibitor of HTR, whereas CP 55,940 was most effective against ESR. The ID(50) potency order of cannabinoids in blocking the HTR is: HU-210 > CP 55,940 > WIN 55,212-2 > Delta(9)-THC > Delta(8)-THC, which is identical to their published order of potency in producing the tetrad of behaviors in mice. On the other hand, they had the following ID(50) potency order against the ESR: CP 55,940 > HU-210 > WIN 55,212-2 > Delta(9)-THC > Delta(8)-THC. The tested cannabinoids were 3-30 times more potent in preventing the ESR than the HTR. The data show that cannabinoids inhibit 5-HT(2A) receptor-mediated functions in a potent but differential manner.
机译：我们最近显示，在未吸毒的小鼠中，选择性大麻素CB（1）受体拮抗剂SR 141716A产生强劲的头部抽搐反应（HTR）和耳抓反应（ESR）频率。选择性的5-HT（2A / C）受体拮抗剂SR 46349B强力阻止了这两种行为。选择性5-HT（2A / C）激动剂（如DOI）也会在小鼠中产生这些行为。本研究的目的是：（1）研究Delta（9）-四氢大麻酚（Delta（9）-THC）及其类似物[Delta（8）-四氢大麻酚（Delta（8）-THC），HU-210 ，CP 55,940和WIN 55,212-2]可以防止DOI诱导的行为，并且（2）观察这些大麻素相对于它们抑制DOI诱导的HTR和ESR的ID（50）效能顺序是否存在任何相关性出版的ED（50）效能图谱在小鼠中产生行为四重态。因此，在0分钟时，向不同组的小鼠腹膜内注射媒介物或不同剂量的以下大麻素：Delta（9）-THC（0.25-20 mg / kg），Delta（8）-THC（2.5-20 mg / kg），HU-210（0.02-0.5 mg / kg），CP 55,940（0.004-0.5 mg / kg）和WIN 55,212-2（0.5-10 mg / kg）。二十分钟后，每只小鼠腹膜内注射DOI（1 mg / kg），并在接下来的20分钟内记录DOI诱导的行为频率（平均+/- S.E.M.）。测试的大麻素以剂量依赖性方式降低了DOI诱导的HTR和ESR的频率。 HU-210是最有效的HTR抑制剂，而CP 55,940对ESR最有效。大麻素阻断HTR的ID（50）效能顺序为：HU-210> CP 55,940> WIN 55,212-2> Delta（9）-THC> Delta（8）-THC，这与它们公布的效能顺序相同在小鼠中产生四肢行为。另一方面，它们针对ESR具有以下ID（50）效能顺序：CP 55,940> HU-210> WIN 55,212-2> Delta（9）-THC> Delta（8）-THC。所测试的大麻素在预防ESR方面的功效是HTR的3-30倍。数据显示，大麻素以有效但有区别的方式抑制5-HT（2A）受体介导的功能。

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