Pelloux Yann, Baunez Christelle
Institut de Neurosciences de la Timone, UMR7289, CNRS & Aix-Marseille Université, 27, Boulevard Jean Moulin, 13005, Marseille, France.
National Institute on Drug Abuse Intramural Research Program, 51 Bayview Blvd #200, Baltimore, MD, 21224, USA.
Psychopharmacology (Berl). 2017 Jul;234(14):2127-2137. doi: 10.1007/s00213-017-4618-5. Epub 2017 Apr 11.
The subthalamic nucleus (STN) has only recently been considered to have a role in reward processing. In rats, inactivation of the STN by lesion or high-frequency stimulation (HFS) decreases motivation for cocaine but increases motivation for sucrose. For ethanol, the effect of STN lesion depends on the individual's baseline intake; decreasing motivation for ethanol in rats with lower ethanol intake, while increasing motivation for ethanol in rats with higher-but still limited-ethanol intake. However, the involvement of the STN in behaviour more closely resembling some aspects of alcohol use disorder has not been assessed. This study aimed to determine the effect of STN lesions on the escalation of ethanol intake, subsequent increases in the motivation to "work" for ethanol and the choice of ethanol over a non-drug alternative.
We found that STN lesion prevented increases in ethanol intake observed during intermittent ethanol access and after a long period of ethanol privation. STN lesion also decreased the motivation to work for ethanol after escalated intake. Surprisingly, STN lesion increased the choice of alcohol over saccharin. This was associated with a blunting of the hedonic responses to the taste of the reinforcement alternatives.
These results evidence the involvement of the STN in different ethanol-motivated behaviours and therefore position the STN as an interesting target for the treatment of alcohol use disorders.
直到最近，人们才认为丘脑底核（STN）在奖赏处理中发挥作用。在大鼠中，通过损伤或高频刺激（HFS）使STN失活会降低对可卡因的动机，但会增加对蔗糖的动机。对于乙醇，STN损伤的影响取决于个体的基线摄入量；在乙醇摄入量较低的大鼠中会降低对乙醇的动机，而在乙醇摄入量较高但仍有限的大鼠中会增加对乙醇的动机。然而，尚未评估STN在更类似于酒精使用障碍某些方面的行为中的作用。本研究旨在确定STN损伤对乙醇摄入量增加、随后为获取乙醇“工作”的动机增加以及在乙醇与非药物替代品之间选择乙醇的影响。
我们发现，STN损伤可防止在间歇性给予乙醇期间以及长期乙醇剥夺后观察到的乙醇摄入量增加。STN损伤还会降低摄入量增加后为获取乙醇而工作的动机。令人惊讶的是，STN损伤增加了对酒精而非糖精的选择。这与对强化替代品味道的享乐反应减弱有关。
这些结果证明STN参与了不同的由乙醇驱动的行为，因此将STN定位为治疗酒精使用障碍的一个有趣靶点。
