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首页> 外文期刊>The European Journal of Neuroscience >Chronic BMY7378 treatment alters behavioral circadian rhythms
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Chronic BMY7378 treatment alters behavioral circadian rhythms

机译：慢性BMY7378治疗改变了行为昼夜节律

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The mammalian circadian clock is synchronized to the day : night cycle by light. Serotonin modulates the circadian effects of light, with agonists inhibiting response to light and antagonists enhancing responses to light. A special class of serotonergic compounds, the mixed 5-HT1A agonist/antagonists, potentiates light-induced phase advances by up to 400% when administered acutely. In this study, we examine the effects of one of these mixed 5-HT1A agonist/antagonists, BMY7378, when administered chronically. Thirty adult male hamsters were administered either vehicle or BMY7378 via surgically implanted osmotic mini pumps over a period of 28 days. In a light : dark cycle, chronic BMY7378 advanced the phase angle of entrainment, prolonged the duration of the active phase and attenuated the amplitude of the wheel-running rhythm during the early night. In constant darkness, chronic treatment with BMY7378 significantly attenuated light-induced phase advances, but had no significant effect on light-induced phase delays. Non-photic phase shifts to daytime administration of a 5-HT1A/7 agonist were also attenuated by chronic BMY7378 treatment. qRT-PCR analysis revealed that chronic BMY7378 treatment upregulated mRNA for 5-HT1A and 5-HT1B receptors in the hypothalamus and downregulated mRNA for 5-HT1A and monoamine oxidase-A in the brainstem. These results highlight adaptive changes of serotonin receptors in the brain to chronic treatment with BMY7378 and link such up- and downreg-ulation to changes in important circadian parameters. Such long-term changes to the circadian system should be considered when patients are treated chronically with drugs that alter serotonergic function.
机译：哺乳动物昼夜时钟与当天同步：夜周期通过光线。血清素调节光的昼夜宿主，具有抑制对光和拮抗剂的反应增强对光的反应的反应。一类特殊的血清on酮化合物，混合的5-HT1A激动剂/拮抗剂，当急性施用时，增强光诱导的相位高达400％。在这项研究中，当长期施用时，我们检查这些混合5-HT1A激动剂/拮抗剂BMY7378中的一个的效果。在28天的时间内通过手术植入的渗透肌肉迷你泵进行三十个成年雄仓鼠。在一个灯光下：暗循环，慢性BMY7378先进的夹带相角，延长了主动相的持续时间，并在初期衰减了车轮运行节奏的幅度。在恒定的黑暗中，慢性处理BMY7378显着减弱了光诱导的相进程，但对光诱导的相位延迟没有显着影响。通过慢性BMY7378治疗还衰减到白天施用5-HT1A / 7激动剂的白天施用。 QRT-PCR分析显示，慢性BMY7378治疗脑下下丘脑中5-HT1A和5-HT1B受体的上调mRNA，5-HT1A和单胺氧化酶-A中的下调mRNA。这些结果突出了大脑中血清素受体的适应性变化与BMY7378的慢性治疗，并将这种升级和下调与重要的昼夜参数的变化联系起来。当患者慢性治疗患者用改变血清onOnergic功能的药物治疗时，应考虑对昼夜昼夜的改变。

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