Orexin-1 receptor signalling in the prelimbic cortex and ventral tegmental area regulates cue-induced reinstatement of ethanol-seeking in iP rats
Orexin-1 receptor signalling in the prelimbic cortex and ventral tegmental area regulates cue-induced reinstatement of ethanol-seeking in iP rats
复制标题
DOI：
10.1111/adb.12251
复制
发表时间：
2016-05-01
影响因子：
3.4
通讯作者：
Lawrence, Andrew John
中科院分区：
文献类型：
--
作者：
Brown, Robyn Mary;Kim, Andrezza K.;Lawrence, Andrew John
食欲素（下丘脑分泌素）是支配整个神经轴的下丘脑神经肽，包括前边缘皮层和腹侧被盖区，并与寻求酒精的行为有关。本研究旨在利用食欲素-1 （OX1）受体拮抗剂SB-334867检测前边缘皮质和腹侧被皮层OX1受体在线索诱导的乙醇寻求恢复中的作用。乙醇偏好大鼠（iP）被训练成在存在奖励相关提示的情况下自我管理乙醇（10% v/v, FR3）或蔗糖（0.2- 1% w/v, FR3），然后植入留置引导管。然后对大鼠进行11天的灭绝训练。在试验日，给大鼠微量注射载药或SB-334867 （3g/侧），并给予奖励相关提示以沉淀恢复。结果表明，注入SB-334867可减弱线索诱导的乙醇寻求恢复，但对蔗糖寻求无抑制作用。腹侧被盖区OX1的拮抗也减弱了线索诱导的乙醇寻求的恢复。这些发现表明，位于大脑前边缘皮层和腹侧被盖区的OX1受体是驱动线索介导的酒精寻求行为的回路的一部分。
Orexins (hypocretins) are hypothalamic neuropeptides that innervate the entire neuraxis, including the prelimbic cortex and ventral tegmental area and have been implicated in ethanol-seeking behaviour. The present study aimed to use the orexin-1 (OX1) receptor antagonist SB-334867 to examine the role of prelimbic cortex and ventral tegmental area OX1 receptors in cue-induced reinstatement of ethanol-seeking. Ethanol-preferring rats (iP) rats were trained to self-administer ethanol (10percent v/v, FR3) or sucrose (0.2-1percent w/v, FR3) in the presence of reward-associated cues before being implanted with indwelling guide cannulae. Rats then underwent extinction training for 11 days. On test days, rats were given a microinjection of vehicle or SB-334867 (3g/side) and presented with reward-associated cues to precipitate reinstatement. Results show SB-334867 infused into the prelimbic cortex attenuated cue-induced reinstatement of ethanol-seeking, but not sucrose-seeking. OX1 antagonism in the ventral tegmental area also attenuated cue-induced reinstatement of ethanol-seeking. These findings suggest that OX1 receptors located in the prelimbic cortex and ventral tegmental area are part of a circuit driving cue-mediated ethanol-seeking behaviour.