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5-羟色胺 2C 受体强烈调节苯丙胺类致幻剂诱导的小鼠头部抽动反应。

The serotonin 2C receptor potently modulates the head-twitch response in mice induced by a phenethylamine hallucinogen.

机构信息

Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.

出版信息

Psychopharmacology (Berl). 2010 Apr;209(2):163-74. doi: 10.1007/s00213-010-1784-0. Epub 2010 Feb 19.

DOI:10.1007/s00213-010-1784-0
PMID:20165943
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2868321/
Abstract

RATIONALE

Hallucinogenic serotonin 2A (5-HT(2A)) receptor partial agonists, such as (+ or -)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), induce a frontal cortex-dependent head-twitch response (HTR) in rodents, a behavioral proxy of a hallucinogenic response that is blocked by 5-HT(2A) receptor antagonists. In addition to 5-HT(2A) receptors, DOI and most other serotonin-like hallucinogens have high affinity and potency as partial agonists at 5-HT(2C) receptors.

OBJECTIVES

We tested for involvement of 5-HT(2C) receptors in the HTR induced by DOI.

RESULTS

Comparison of 5-HT(2C) receptor knockout and wild-type littermates revealed an approximately 50% reduction in DOI-induced HTR in knockout mice. Also, pretreatment with either the 5-HT(2C) receptor antagonist SB206553 or SB242084 eradicated a twofold difference in DOI-induced HTR between the standard inbred mouse strains C57BL/6J and DBA/2J, and decreased the DOI-induced HTR by at least 50% in both strains. None of several measures of 5-HT(2A) receptors in frontal cortex explained the strain difference, including 5-HT(2A) receptor density, Galpha(q) or Galpha(i/o) protein levels, phospholipase C activity, or DOI-induced expression of Egr1 and Egr2. 5-HT(2C) receptor density in the brains of C57BL/6J and DBA/2J was also equivalent, suggesting that 5-HT(2C) receptor-mediated intracellular signaling or other physiological modulators of the HTR may explain the strain difference in response to DOI.

CONCLUSIONS

We conclude that the HTR to DOI in mice is strongly modulated by 5-HT(2C) receptor activity. This novel finding invites reassessment of hallucinogenic mechanisms involving 5-HT(2) receptors.

摘要

原理

致幻性血清素 2A（5-HT（2A））受体部分激动剂，如（+/-）-1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷盐酸盐（DOI），在啮齿动物中诱导额皮质依赖的头部抽搐反应（HTR），这是一种致幻反应的行为替代物，可被 5-HT（2A）受体拮抗剂阻断。除了 5-HT（2A）受体外，DOI 和大多数其他血清素样致幻剂对 5-HT（2C）受体具有高亲和力和效力作为部分激动剂。

目的

我们测试了 5-HT（2C）受体在 DOI 诱导的 HTR 中的作用。

结果

5-HT（2C）受体敲除和野生型同窝仔鼠的比较显示，DOI 诱导的 HTR 在敲除鼠中减少了约 50%。此外，5-HT（2C）受体拮抗剂 SB206553 或 SB242084 的预处理消除了标准近交系 C57BL/6J 和 DBA/2J 之间 DOI 诱导的 HTR 之间的两倍差异，并使两种品系的 DOI 诱导的 HTR 减少至少 50%。额皮质中 5-HT（2A）受体的几种测量方法均不能解释品系差异，包括 5-HT（2A）受体密度、Galpha(q) 或 Galpha(i/o) 蛋白水平、磷脂酶 C 活性或 DOI 诱导的 Egr1 和 Egr2 的表达。C57BL/6J 和 DBA/2J 大脑中的 5-HT（2C）受体密度也相等，这表明 5-HT（2C）受体介导的细胞内信号转导或 HTR 的其他生理调节剂可能解释了对 DOI 的反应的品系差异。

结论

我们得出结论，小鼠对 DOI 的 HTR 受到 5-HT（2C）受体活性的强烈调节。这一新发现邀请重新评估涉及 5-HT（2）受体的致幻机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7f7/2868321/1c8e2128e214/nihms194572f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7f7/2868321/355015bcf85e/nihms194572f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7f7/2868321/955aaef4a93e/nihms194572f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7f7/2868321/6568c69b774f/nihms194572f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7f7/2868321/95748bfe61d6/nihms194572f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7f7/2868321/462a7a69db0d/nihms194572f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7f7/2868321/293938b8af43/nihms194572f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7f7/2868321/1c8e2128e214/nihms194572f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7f7/2868321/355015bcf85e/nihms194572f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7f7/2868321/955aaef4a93e/nihms194572f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7f7/2868321/6568c69b774f/nihms194572f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7f7/2868321/95748bfe61d6/nihms194572f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7f7/2868321/462a7a69db0d/nihms194572f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7f7/2868321/293938b8af43/nihms194572f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7f7/2868321/1c8e2128e214/nihms194572f7.jpg

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