Oxytocin Reduces Cocaine Cued Fos Activation in a Regionally Specific Manner.
Oxytocin Reduces Cocaine Cued Fos Activation in a Regionally Specific Manner.
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DOI：
10.1093/ijnp/pyx058
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发表时间：
2017-10-01
期刊：
影响因子：
--
通讯作者：
Reichel CM
中科院分区：
文献类型：
--
作者：
Leong KC;Freeman LR;Berini CR;Ghee SM;See RE;Reichel CM
催产素可能是一种治疗多种神经精神疾病的可能方法，包括可卡因成瘾。关于催产素对各种与药物成瘾有关的大脑区域的特定部位的影响，人们知之甚少。此外，催产素对成瘾回路中神经功能的性二态效应尚未确定。在这里，我们研究了Fos表达可卡因线索恢复在雄性和雌性大鼠。对雄性和雌性大鼠进行自我给药、消退和恢复试验。在测试日，大鼠给予催产素或车辆，并测量杠杆按压响应条件可卡因线索。灌流大鼠，并在中央杏仁核，内侧前额叶皮质，丘脑底核和丘脑核的Fos染色测量。Fos/催产素双标记出现在下丘脑室旁核。大鼠恢复可卡因线索相对于灭绝反应和催产素减少可卡因寻求。催产素结合应急提示介绍增加Fos+催产素细胞体的下丘脑室旁核内相对于车辆。催产素给药后，中央杏仁核的Fos表达显著增加。催产素逆转线索诱导的Fos在内侧前额叶皮层，丘脑底核，核芯的表达。中枢催产素输注也减弱了可卡因寻求的恢复。催产素减少了恢复的可卡因寻求，增加了下丘脑室旁核和中央杏仁核的Fos激活，但使内侧前额叶皮质、伏隔核核心和丘脑底核中线索诱导的Fos激活正常化，从而表现出区域特异性激活模式。催产素对可卡因寻求和Fos激活的影响没有性别差异，表明催产素作用于对男性和女性恢复可卡因寻求至关重要的相似中枢神经回路。
Oxytocin may be a possible treatment for multiple neuropsychiatric disorders, including cocaine addiction. Little is known about the site-specific effects of oxytocin on various drug addiction-related brain regions. Furthermore, sexually dimorphic effects of oxytocin on neural function in the addiction circuit have not been established. Here, we studied Fos expression following cocaine-cued reinstatement in both male and female rats. Male and female rats underwent self-administration, extinction, and reinstatement tests. On test days, rats were given oxytocin or vehicle, and lever pressing was measured in response to conditioned cocaine cues. Rats were perfused and Fos staining measured in the central amygdala, medial prefrontal cortex, nucleus accumbens core, and subthalamic nucleus. Fos/oxytocin double labeling occurred in the paraventricular nucleus of the hypothalamus. Rats reinstated to cocaine cues relative to extinction responding and oxytocin reduced cocaine seeking. Oxytocin combined with contingent cue presentations increased Fos+ oxytocin cell bodies within the paraventricular nucleus of the hypothalamus relative to vehicle. Fos expression robustly increased in the central amygdala following oxytocin administration. Oxytocin reversed cue-induced Fos expression in the medial prefrontal cortex, nucleus accumbens core, and subthalamic nucleus. Central oxytocin infusion also attenuated reinstated cocaine seeking. Oxytocin decreased reinstated cocaine seeking, increased Fos activation in the paraventricular nucleus of the hypothalamus and central amygdala, but normalized cue-induced Fos activation in the medial prefrontal cortex, nucleus accumbens core, and subthalamic nucleus, thereby demonstrating regionally specific activation patterns. No sex differences were seen for the effects of oxytocin on cocaine seeking and Fos activation, indicating that oxytocin acts on similar central neural circuits critical to reinstated cocaine seeking in both males and females.
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影响因子：
4.2
作者：
Becker, Jill B.;McClellan, Michele L.;Reed, Beth Glover
通讯作者：
Reed, Beth Glover
影响因子：
3.4
作者：
Georgiou, Polymnia;Zanos, Panos;Bailey, Alexis
通讯作者：
Bailey, Alexis
影响因子：
2.7
作者：
Feltenstein, Matthew W.;See, Ronald E.
通讯作者：
See, Ronald E.
影响因子：
5.6
作者：
Georgiou, Polymnia;Zanos, Panos;Bailey, Alexis
通讯作者：
Bailey, Alexis
影响因子：
10.6
作者：
Cox BM;Bentzley BS;Regen-Tuero H;See RE;Reichel CM;Aston-Jones G
通讯作者：
Aston-Jones G