Rodrigues Samanta, Salum Cristiane, Ferreira Tatiana L
Centro de Matemática Computação e Cognição, Universidade Federal do ABC, São Bernardo do Campo, Brazil.
J Psychopharmacol. 2017 Apr;31(4):505-513. doi: 10.1177/0269881116686879. Epub 2017 Jan 24.
Prepulse inhibition (PPI) is a behavioral test in which the startle reflex response to a high-intensity stimulus (pulse) is inhibited by the prior presentation of a weak stimulus (prepulse). The classic neural circuitry that mediates startle response is localized in the brainstem; however, recent studies point to the contribution of structures involved in higher cognitive functions in regulating the sensorimotor gating, particularly forebrain regions innervated by dopaminergic nuclei. The aim of the present study was to verify the role of dorsal striatum (DS) and dopaminergic transmitting mediated by D1 and D2 receptors on PPI test in rats. DS inactivation induced by muscimol injection did not affect PPI (%PPI and startle response), although it impaired the locomotor activity and caused catalepsy. Infusion of D1-like antagonist SCH23390 impaired %PPI but did not disturb the startle response and locomotor activity evaluated immediately after PPI test. D2 antagonist microinjection (sulpiride) did not affect %PPI and startle response, but impaired motor activity. These results point to an important role of DS, probably mediated by direct basal ganglia pathway, on modulation of sensorimotor gating, in accordance with clinical studies showing PPI deficits in schizophrenia, Tourette syndrome, and compulsive disorders - pathologies related to basal ganglia dysfunctions.
前脉冲抑制(PPI)是一种行为测试,其中对高强度刺激(脉冲)的惊吓反射反应会被先前呈现的弱刺激(前脉冲)所抑制。介导惊吓反应的经典神经回路位于脑干;然而,最近的研究指出,参与更高认知功能的结构在调节感觉运动门控方面发挥了作用,特别是由多巴胺能核支配的前脑区域。本研究的目的是验证大鼠背侧纹状体(DS)以及由D1和D2受体介导的多巴胺能传递在PPI测试中的作用。注射蝇蕈醇诱导的DS失活并未影响PPI(%PPI和惊吓反应),尽管它损害了运动活性并导致了僵住症。注入D1样拮抗剂SCH23390会损害%PPI,但不会干扰PPI测试后立即评估的惊吓反应和运动活性。注射D2拮抗剂(舒必利)不会影响%PPI和惊吓反应,但会损害运动活性。这些结果表明,DS可能通过直接的基底神经节通路介导,在感觉运动门控的调节中起重要作用,这与临床研究结果一致,这些研究表明精神分裂症、妥瑞氏症和强迫症(与基底神经节功能障碍相关的疾病)存在PPI缺陷。