Institute of Pharmacology, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia.
Institute of Pharmacology, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia.
Neuropharmacology. 2019 Jan;144:184-192. doi: 10.1016/j.neuropharm.2018.10.034. Epub 2018 Oct 24.
Trace Amine Associated Receptor 1 (TAAR1) is a novel pharmacological target. TAAR1 are well-documented to play a modulatory role in the dopaminergic system. In spite of a growing number of studies of TAAR1 effects, little is still known about the behavioral pharmacology of TAAR1 ligands, including effects of repeated TAAR1 agonist administration. The present study appears to be the first that estimated the action of TAAR1 agonists on schedule-induced polydipsia, a type of adjunctive behavior, which is considered to be useful for evaluating certain aspects of obsessive-compulsive and related disorders (OCD) and schizophrenia. Our results have demonstrated that the wide range of RO5263397, the highly selective partial TAAR1 agonist, doses (1-10 mg/kg) attenuated the polydipsia induced by two different schedules of food delivery in rats. The effect remained unchanged for the 7 days of repeated treatment. However, the highest tested doses of RO5263397 (6 and 10 mg/kg) decreased the vertical locomotor activity of the animals and the volume of water intake of thirsty rats following the acute treatment. Also, though, the repeated RO5263397 administration is exhibited to diminish the volume of consumed water and weight of rats without SIP, on the other hand, the tolerance was observed to these drug effects. In general, the RO5263397 decreases specifically the adjunctive drinking and this effect is maintained with repeated drug administration without the development of tolerance. The interpretation of these results as an evidence for the RO5263397 anticompulsive-like action, however, should be taken with caution because the drug also influenced the drinking behavior and only weakly affected the other parameters of SIP used to reveal the potential anticompulsive-like effects of drugs.
追踪胺相关受体 1（TAAR1）是一个新型的药理学靶点。TAAR1 在多巴胺能系统中发挥调节作用已得到充分证实。尽管越来越多的研究关注 TAAR1 的作用，但对于 TAAR1 配体的行为药理学，包括重复 TAAR1 激动剂给药的影响，我们仍然知之甚少。本研究似乎是首次评估 TAAR1 激动剂对饮食诱导性多饮（一种辅助行为）的作用，该行为被认为可用于评估强迫症和相关障碍（OCD）和精神分裂症的某些方面。我们的研究结果表明，广泛范围的 RO5263397（高度选择性的部分 TAAR1 激动剂）剂量（1-10mg/kg）可减轻两种不同食物递送方案诱导的大鼠多饮。重复治疗 7 天，该效果保持不变。然而，测试的最高剂量的 RO5263397（6 和 10mg/kg）降低了动物的垂直运动活性和口渴大鼠急性治疗后的饮水量。此外，尽管重复给予 RO5263397 可减少 SIP 大鼠的饮水量和体重，但对这些药物作用表现出耐受性。总的来说，RO5263397 特异性地减少了辅助性饮水，并且这种效果在重复给药时得以维持，而没有出现耐受性。然而，应谨慎解释这些结果，因为该药物还影响了饮水行为，并且仅对用于揭示药物潜在抗强迫作用的 SIP 的其他参数产生微弱影响。
