Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, Pittsburgh, PA, USA.
Learning in Biological and Artificial Systems Research Group, Institute of Physiology, Pittsburgh, PA, USA.
Int J Neuropsychopharmacol. 2022 Aug 4;25(7):590-599. doi: 10.1093/ijnp/pyac024.
The ventral pallidum (VP) is a dopaminoceptive forebrain structure regulating the ventral tegmental area (VTA) dopaminergic population activity. We have recently demonstrated that in the VP, the D2-like dopamine (DA) receptor agonist quinpirole dose dependently facilitates memory consolidation in inhibitory avoidance and spatial learning. According to our hypothesis, quinpirole microinjected into the VP can modulate the VTA DAergic activity and influence motivation and learning processes of rats.
Quinpirole was microinjected at 3 different doses into the VP of male rats, and controls received vehicle. Single unit recordings were employed to assess VTA DAergic activity. To investigate the possible reinforcing or aversive effect of quinpirole in the VP, the conditioned place preference paradigm was used.
Our results showed that intra-VP quinpirole microinjection regulates VTA DAergic neurons according to an inverted U-shaped dose-response curve. The largest dose of quinpirole decreased the population activity and strongly reduced burst activity of the DAergic neurons in the first hour after its application. In contrast, the 2 smaller doses increased DA population activity, but their effect started with a delay 1 hour after their microinjection. The CPP experiments revealed that the largest dose of quinpirole in the VP induced place aversion in the rats. Furthermore, the largest dose of quinpirole induced an acute locomotor activity reduction, while the medium dose led to a long-duration increase in locomotion.
In summary, quinpirole dose dependently regulates VTA DAergic activity as well as the motivation and motor behavior of the rats at the level of the VP.
腹侧苍白球（VP）是一种调节腹侧被盖区（VTA）多巴胺能神经元群体活动的多巴胺能感受前脑结构。我们最近的研究表明，在 VP 中，D2 样多巴胺（DA）受体激动剂喹吡罗可剂量依赖性地促进抑制性回避和空间学习的记忆巩固。根据我们的假设，注射到 VP 中的喹吡罗可以调节 VTA 的 DA 能活动，并影响大鼠的动机和学习过程。
将喹吡罗以 3 种不同剂量微注射到雄性大鼠的 VP 中，对照组给予载体。采用单细胞记录评估 VTA 的 DA 能活动。为了研究喹吡罗在 VP 中可能具有强化或厌恶作用，使用条件性位置偏好范式进行研究。
我们的结果表明，VP 内的喹吡罗微注射根据倒 U 形剂量反应曲线调节 VTA 的 DA 能神经元。最大剂量的喹吡罗在应用后 1 小时内降低了神经元群体活动，并强烈减少了 DA 能神经元的爆发活动。相比之下，较小的两种剂量增加了 DA 神经元的群体活动，但它们的作用在微注射后 1 小时才开始显现。CPP 实验表明，VP 中的最大剂量喹吡罗诱导大鼠产生位置厌恶。此外，最大剂量的喹吡罗诱导急性运动活性降低，而中等剂量导致长时间运动活性增加。
综上所述，喹吡罗在 VP 水平上可剂量依赖性地调节 VTA 的 DA 能活动以及大鼠的动机和运动行为。
