简介:腹侧苍白球(VP)是边缘基底神经节回路的中心,控制食欲(接近)和厌恶(回避)动机行为。然而,VP在病理方面的参与仍不清楚,特别是在不同动机功能障碍的行为表达中。本研究旨在探讨VP如何通过相反的GABA能功能障碍促进异常行为的表达。方法:通过向猴子注射麝香酚(GABAA激动剂)和双瓜碱(GABAA拮抗剂)来诱导相反的GABA能功能障碍。我们确定了这两种物质对六只猴子在实验室椅和自由移动的家庭笼子环境中自我启动行为的影响,在两个动物中,在食欲和厌恶的情况下执行回避任务。结果:在VP中注射双子胶引起的自我启动行为具有强迫行为,例如重复修饰和自我咬伤,麝香酚注射会引起冲动行为,包括在实验室椅子环境中的肢体运动和在自由移动环境中的探索行为。在回避接近任务中观察到更具体的行为效应。麝香酚注射会引起过早的反应和错误的屏幕触摸,这是冲动和注意力障碍的特征,而在一个令人厌恶的环境中,向VP注射双微线增加了被动回避(非启动动作)和任务逃避,暗示是焦虑症.结论:这些结果表明,激活或阻断VP中的GABA能传递会损害动机行为。此外,这些相反的障碍产生的行为表达表明,VP可能与焦虑驱动的强迫症有关,如强迫症,以及由注意力缺陷或寻求奖励引起的冲动性障碍,如ADHD或冲动控制障碍所示。
Introduction: The ventral pallidum (VP) is central in the limbic Basal Ganglia circuit, controlling both appetitive (approach) and aversive (avoidance) motivated behaviors. Nevertheless, VP involvement in pathological aspects remains unclear, especially in the behavioral expression of different motivational dysfunctions. This study aimed to investigate how the VP contributes to the expression of abnormal behaviors via opposite GABAergic dysfunctions. Methods: Opposite GABAergic dysfunctions were induced by injecting muscimol (a GABAA agonist) and bicuculline (a GABAA antagonist) into monkeys. We determined the effects of both substances on self-initiated behaviors in lab-chair and in free-moving home-cage contexts in six monkeys, and in two animals performing an approach-avoidance task in appetitive and aversive contexts. Results: While the self-initiated behaviors induced by bicuculline injections in VP were characterized by compulsive behaviors such as repetitive grooming and self-biting, muscimol injections induced impulsive behaviors including limb movements in a lab-chair context and exploration behaviors in a free-moving context. More specific behavioral effects were observed in the approach-avoidance task. The muscimol injections induced premature responses and erroneous screen touches, which characterize impulsive and attention disorders, while the bicuculline injections into the VP increased passive avoidance (non-initiated action) and task-escape in an aversive context, suggesting an anxiety disorder. Conclusions: These results show that activating or blocking GABAergic transmission in the VP impairs motivated behaviors. Furthermore, the behavioral expressions produced by these opposite disturbances show that the VP could be involved in anxiety-driven compulsive disorders, such as OCD, as well as in impulsive disorders motivated by attention deficits or reward-seeking, as seen in ADHD or impulse control disorders.