A Paradoxical Locomotor Response in Serotonin 5-HT2C Receptor Mutant Mice
A Paradoxical Locomotor Response in Serotonin 5-HT2C Receptor Mutant Mice
复制标题
血清素 5-HT2C 受体突变小鼠的矛盾运动反应
DOI：
10.1523/jneurosci.20-08-j0003.2000
复制
发表时间：
2000
期刊：
影响因子：
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通讯作者：
L. Tecott
中科院分区：
文献类型：
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作者：
L. Heisler;L. Tecott
Paradoxical behavioral responses to nonselective neuropsychiatric drugs are frequently encountered and poorly understood. We report that a single receptor gene mutation produces a paradoxical response to the nonspecific serotonin receptor agonist m-chlorophenylpiperazine (mCPP). Although this compound normally suppresses locomotion, it produces hyperactivity in mice bearing a targeted mutation of the 5-HT(2C) receptor gene. This effect was blocked by pretreatment with a 5-HT(1B) receptor antagonist, indicating that the behavioral consequences of mCPP-induced 5-HT(1B) receptor stimulation are unmasked in animals devoid of 5-HT(2C) receptor function. Furthermore, this paradoxical response to mCPP was reproduced in wild-type C57BL/6 mice by previous pharmacological blockade of 5-HT(2C) receptors, indicating that the mutant phenotype does not result from perturbations of brain development. These effects of 5-HT1B and 5-HT(2C) receptor antagonists likely reflected blockade of pharmacological actions of mCPP, because these compounds did not alter locomotor activity levels when administered alone. Thus, mCPP interacts with distinct 5-HT receptor targets that produce opposing effects on locomotor activity levels. A paradoxical behavioral response is produced by the genetic inactivation of the target that produces the prevailing effect of the drug in the wild-type animal. This genetically based paradoxical drug effect provides a model for considering the effects of genetic load on neurobehavioral responses to drugs.
DOI：
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发表时间：
1989-04
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
I. Lucki;H. R. Ward;A. Frazer
通讯作者：
I. Lucki;H. R. Ward;A. Frazer
创伤后应激障碍中的去甲肾上腺素能和血清素能功能。
影响因子：
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作者：
Southwick,SM;Krystal,JH;Bremner,JD;Morgan3rd,CA;Nicolaou,AL;Nagy,LM;Johnson,DR;Heninger,GR;Charney,DS
通讯作者：
Charney,DS