5-HT1B mRNA expression after chronic social stress.
5-HT1B mRNA expression after chronic social stress.
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DOI：
10.1016/j.bbr.2011.06.016
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发表时间：
2011-10-31
影响因子：
2.7
通讯作者：
Neumaier, John F.
中科院分区：
文献类型：
--
作者：
Furay, Amy R.;McDevitt, Ross A.;Miczek, Klaus A.;Neumaier, John F.
长期的压力导致易患抑郁症和吸毒成瘾。5-羟色胺能系统的功能已被发现被慢性应激改变，这些变化可能在应激相关的药物渴求复发中发挥重要作用。5-HT1B受体在伏核投射神经元中表达，调节药物奖赏机制，有证据表明应激改变了这些受体的调节和功能。为了研究这些受体在整合应激对奖励机制的影响中的作用，我们研究了慢性或急性社会失败应激(SDS)是否调节背侧和腹侧纹状体的5-HT1B mRNA，这两个区域对于整合环境应激对奖励行为的影响至关重要。在第三个实验中，测量了5-HT1B mRNA对另一种急性应激源--不可避免的尾部电击--的调节。我们的结果表明，间歇的和每天的SDS程序可以减轻体重增加，诱导肾上腺肥大，并降低对糖精的偏好，糖精是正常大鼠更喜欢的甜味剂。伏隔核5-HT1B受体基因表达水平有每天升高的趋势，但不是间歇性的。因此，在接下来的实验中，我们更详细地检测了每天的十二烷基硫酸钠，发现它增加了伏隔嘴核5-HT1B受体mRNA的表达，这是一个特别与奖励功能相关的区域。急性十二烷基硫酸钠和急性尾部应激对纹状体5-HT1B基因表达均无显著影响。由于伏隔核壳神经元5-HT1B受体的表达增加可以促进可卡因和酒精的奖赏机制，内源性5-HT1B mRNA的这种适应可能参与了与十二烷基硫酸钠相关的成瘾易感性的增加。
Chronic stress contributes to vulnerability for depression and drug addiction. The function of the serotonergic system has been found to be modified by chronic stress and these changes may play an important role in stress-related relapses to drug craving. The 5-HT1B receptor is expressed in nucleus accumbens projection neurons and modulates drug reward mechanisms and there is evidence suggesting that stress alters the regulation and function of these receptors. To examine the role of these receptors in integrating the effects of stress on reward mechanisms, we examined whether chronic or acute social defeat stress (SDS) regulates 5-HT1B mRNA in dorsal and ventral striatum, regions that are critical for integrating the effects of environmental stresses on reward motivated behavior. In a third experiment, 5-HT1B mRNA regulation in response to another acute stressor, inescapable tailshock, was measured. Our results indicate that intermittent and daily SDS procedures attenuated body weight gain, induced adrenal hypertrophy, and reduced the preference for saccharin, a sweet solution preferred by normal rats. There was a trend for daily, but not intermittent SDS to increase 5-HT1B receptor mRNA levels in nucleus accumbens. Therefore, in the next experiment, we examined daily SDS in greater detail and found that it increased 5-HT1B receptor mRNA expression in rostral nucleus accumbens shell, an area especially associated with reward functions. Neither acute SDS, nor acute tailshock stress had a significant impact on 5-HT1B mRNA expression in the striatum. Since increased 5-HT1B receptor expression in nucleus accumbens shell neurons can facilitate cocaine and alcohol reward mechanisms, this adaptation in endogenous 5-HT1B mRNA may be involved in the SDS-associated increase in vulnerability for developing addiction.
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