Pelloux Yann, Meffre Julie, Giorla Elodie, Baunez Christelle
Institut de Neurosciences de la Timone, UMR7289, CNRS and Aix-Marseille Université Marseille, France.
Front Behav Neurosci. 2014 Dec 5;8:414. doi: 10.3389/fnbeh.2014.00414. eCollection 2014.
The subthalamic nucleus (STN) belongs to the basal ganglia and is the current target for the surgical treatment of neurological and psychiatric disorders such as Parkinson's Disease (PD) and obsessive compulsive disorders (OCD), but also a proposed site for the treatment of addiction. It is therefore very important to understand its functions in order to anticipate and prevent possible side-effects in the patients. Although the involvement of the STN is well documented in motor, cognitive and motivational processes, less is known regarding emotional processes. Here we have investigated the direct consequences of STN inactivation by excitotoxic lesions on emotional processing and reinforcement in the rat. We have used various behavioral procedures to assess affect for neutral, positive and negative reinforcers in STN lesioned rats. STN lesions reduced affective responses for positive (sweet solutions) and negative (electric foot shock, Lithium Chloride-induced sickness) reinforcers while they had no effect on responses for a more neutral reinforcer (novelty induced place preference (NIPP)). Furthermore, when given the choice between saccharine, a sweet but non caloric solution, and glucose, a more bland but caloric solution, in contrast to sham animals that preferred saccharine, STN lesioned animals preferred glucose over saccharine. Taken altogether these results reveal that STN plays a critical role in emotional processing. These results, in line with some clinical observations in PD patients subjected to STN surgery, suggest possible emotional side-effects of treatments targeting the STN. They also suggest that the increased motivation for sucrose previously reported cannot be due to increased pleasure, but could be responsible for the decreased motivation for cocaine reported after STN inactivation.
丘脑底核(STN)属于基底神经节,是目前治疗帕金森病(PD)和强迫症(OCD)等神经和精神疾病的手术靶点,也是治疗成瘾的一个提议部位。因此,了解其功能对于预测和预防患者可能出现的副作用非常重要。尽管STN在运动、认知和动机过程中的参与已有充分记录,但对其在情绪过程中的作用了解较少。在这里,我们研究了兴奋性毒性损伤使STN失活对大鼠情绪加工和强化的直接影响。我们使用了各种行为程序来评估STN损伤大鼠对中性、积极和消极强化物的情感反应。STN损伤降低了对积极强化物(甜味溶液)和消极强化物(电足部电击、氯化锂诱导的疾病)的情感反应,而对更中性的强化物(新奇诱导的位置偏好(NIPP))的反应没有影响。此外,当在甜味但无热量的糖精溶液和更平淡但有热量的葡萄糖溶液之间进行选择时,与偏好糖精的假手术动物相比,STN损伤的动物更喜欢葡萄糖而不是糖精。综合这些结果表明,STN在情绪加工中起关键作用。这些结果与接受STN手术的PD患者的一些临床观察结果一致,提示针对STN的治疗可能存在情绪副作用。它们还表明,先前报道的对蔗糖动机的增加并非由于愉悦感增加,而是可能导致STN失活后报道的对可卡因动机的降低。