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5-羟色胺（7）受体的失活部分阻断了苯环利定诱导的前脉冲抑制破坏。

Inactivation of the 5-HT(7) receptor partially blocks phencyclidine-induced disruption of prepulse inhibition.

作者信息

Semenova Svetlana, Geyer Mark A, Sutcliffe J Gregor, Markou Athina, Hedlund Peter B

机构信息

Department of Psychiatry, University of California, San Diego, USA.

出版信息

Biol Psychiatry. 2008 Jan 1;63(1):98-105. doi: 10.1016/j.biopsych.2006.12.011. Epub 2007 May 24.

DOI:10.1016/j.biopsych.2006.12.011
PMID:17531208
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2174622/
Abstract

BACKGROUND

Studies have implicated the serotonin (5-HT)(7) receptor in physiological and pathophysiological phenomena, including thermoregulation, central control of micturition and locomotion, regulation of circadian rhythm, sleep, and depression. Further, several antidepressant and antipsychotic drugs have high affinity for the 5-HT(7) receptor.

METHODS

We examined the role of 5-HT(7) receptors in a rodent analogue of sensorimotor gating deficits in schizophrenia: phencyclidine (PCP)-induced disruption of prepulse inhibition (PPI) of acoustic startle. We used mice lacking the 5-HT(7) receptor due to a targeted inactivation of this receptor gene and the selective 5-HT(7) receptor antagonist SB-269970.

RESULTS

SB-269970 did not affect either baseline PPI or PCP-disrupted PPI. There was no difference between 5-HT(7)(+/+) and 5-HT(7)(-/-) mice in startle reactivity or PPI regardless of prepulse intensity (74-82 dB), interstimulus interval (25-500 msec), or pulse intensity (90-120 dB). Nevertheless, disruption of PPI produced by PCP (10 mg/kg) in wild-type mice was reduced in 5-HT(7)(-/-) mice, although it was not affected by the 5-HT(7) antagonist SB-269970. By contrast, the PPI-disruptive effects of apomorphine (5 mg/kg) and amphetamine (7.5 mg/kg) were comparable in both genotypes.

CONCLUSIONS

The results indicate a partial role for the 5-HT(7) receptor in the glutamatergic PPI model of sensorimotor gating deficits in schizophrenia that is sensitive to atypical antipsychotics and no involvement of this receptor in the dopaminergic PPI model that is sensitive to typical antipsychotics. Thus, the 5-HT(7)(-/-) mice may provide a useful tool to study the role of 5-HT(7) receptor in the action of atypical antipsychotic drugs and schizophrenia.

摘要

背景

研究表明，血清素（5-羟色胺，5-HT）（7）受体参与了多种生理和病理生理现象，包括体温调节、排尿和运动的中枢控制、昼夜节律调节、睡眠及抑郁。此外，几种抗抑郁药和抗精神病药对5-HT（7）受体具有高亲和力。

方法

我们在啮齿动物模型中研究了5-HT（7）受体在精神分裂症感觉运动门控缺陷中的作用：苯环利定（PCP）诱导的听觉惊吓前脉冲抑制（PPI）破坏。我们使用了因该受体基因靶向失活而缺乏5-HT（7）受体的小鼠以及选择性5-HT（7）受体拮抗剂SB-269970。

结果

SB-269970对基线PPI或PCP破坏的PPI均无影响。无论前脉冲强度（74 - 82分贝）、刺激间隔（25 - 500毫秒）或脉冲强度（90 - 120分贝）如何，5-HT（7）（+/+）和5-HT（7）（-/-）小鼠在惊吓反应性或PPI方面均无差异。然而，野生型小鼠中由PCP（10毫克/千克）产生的PPI破坏在5-HT（7）（-/-）小鼠中有所减轻，尽管它不受5-HT（7）拮抗剂SB-269970的影响。相比之下，阿扑吗啡（5毫克/千克）和苯丙胺（7.5毫克/千克）对PPI的破坏作用在两种基因型中相当。

结论

结果表明，5-HT（7）受体在对非典型抗精神病药敏感的精神分裂症感觉运动门控缺陷的谷氨酸能PPI模型中起部分作用，而该受体不参与对典型抗精神病药敏感的多巴胺能PPI模型。因此，5-HT（7）（-/-）小鼠可能为研究5-HT（7）受体在非典型抗精神病药物作用及精神分裂症中的作用提供有用工具。

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