Enhanced effects of amphetamine but reduced effects of the hallucinogen, 5-MeO-DMT, on locomotor activity in 5-HT(1A) receptor knockout mice: implications for schizophrenia.
Enhanced effects of amphetamine but reduced effects of the hallucinogen, 5-MeO-DMT, on locomotor activity in 5-HT(1A) receptor knockout mice: implications for schizophrenia.
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DOI：
10.1016/j.neuropharm.2011.04.001
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发表时间：
2011-07
影响因子：
4.7
通讯作者：
Halberstadt, Adam L.
中科院分区：
文献类型：
--
作者：
van den Buuse, Maarten;Ruimschotel, Emma;Martin, Sally;Risbrough, Victoria B.;Halberstadt, Adam L.
5-HT1A(5-HT1A)受体可能在精神分裂症和某些抗精神病药物的作用中起作用。然而，5-HT1A受体与精神分裂症所涉及的大脑系统的相互作用机制尚不清楚。在这里，我们显示了5-HT1A受体基因敲除的小鼠表现出对苯丙胺急性治疗的运动多动增强，苯丙胺是一种广泛使用的精神疾病高多巴胺能机制的动物模型。相反，在基因敲除中，MK-801对运动活动的影响(模拟NMDA受体活性低下)没有变化。致幻剂5-甲氧基-N，N-二甲基色胺(5-MeO-DMT)对5-HT1A受体敲除小鼠的作用明显减弱。阿朴吗啡诱导的PPI中断没有变化，PPI是精神分裂症中出现的感觉门控缺陷的模型。同样，多巴胺转运体(DAT)或多巴胺D1或D2受体的密度没有发生重大变化，这可以解释5-HT1A受体敲除小鼠观察到的行为变化。这些结果扩展了我们对这些受体在精神分裂症方面可能发挥的作用的洞察。以前使用激动剂和拮抗剂药物的研究也表明，5-HT1a受体可能在幻觉中发挥重要作用，并调节大脑中的多巴胺能活动。
Serotonin-1A (5-HT1A) receptors may play a role in schizophrenia and the effects of certain antipsychotic drugs. However, the mechanism of interaction of 5-HT1A receptors with brain systems involved in schizophrenia, remains unclear. Here we show that 5-HT1A receptor knockout mice display enhanced locomotor hyperactivity to acute treatment with amphetamine, a widely used animal model of hyperdopaminergic mechanisms in psychosis. In contrast, the effect of MK-801 on locomotor activity, modeling NMDA receptor hypoactivity, was unchanged in the knockouts. The effect of the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) was markedly reduced in 5-HT1A receptor knockout mice. There were no changes in apomorphine-induced disruption of PPI, a model of sensory gating deficits seen in schizophrenia. Similarly, there were no major changes in density of dopamine transporters (DAT) or dopamine D1 or D2 receptors which could explain the behavioural changes observed in 5-HT1A receptor knockout mice. These results extend our insight into the possible role of these receptors in aspects of schizophrenia. As also suggested by previous studies using agonist and antagonist drugs, 5-HT1A receptors may play an important role in hallucinations and to modulate dopaminergic activity in the brain.
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影响因子：
3.4
作者：
Halberstadt, Adam L.;Buell, Mahalah R.;Masten, Virginia L.;Risbrough, Victoria B.;Geyer, Mark A.
通讯作者：
Geyer, Mark A.
影响因子：
7.6
作者：
Dulawa, SC;Gross, C;Geyer, MA
通讯作者：
Geyer, MA
DOI：
10.1073/pnas.95.18.10734
发表时间：
1998-09-01
影响因子：
11.1
作者：
Parks, CL;Robinson, PS;Toth, M
通讯作者：
Toth, M
影响因子：
3.4
作者：
Chavez, Carolina;Gogos, Andrea;van den Buuse, Maarten
通讯作者：
van den Buuse, Maarten
影响因子：
10.6
作者：
Laruelle, M;Abi-Dargham, A;Innis, R
通讯作者：
Innis, R