Instituto de Neurociências e Comportamento (INeC), Ribeirão Preto, Brazil.
Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, Brazil.
J Psychopharmacol. 2019 Dec;33(12):1524-1532. doi: 10.1177/0269881119862527. Epub 2019 Jul 22.
Intranasally applied dopamine (IN-DA), which likely reaches the brain via nasal-brain pathways and bypasses the blood-brain barrier, has been found to increase extracellular DA and bind to the DA2 transporter in the striatum. Recent studies suggest that DA plays a significant role in the processing of signaled and unconditioned aversive stimulation, including evidence that may attenuate responses to painful input. The purpose of this study was to examine the effects of IN-DA on fear-related behaviors induced by electric shock to the foot or by electrical stimulation of the dorsal periaqueductal gray matter (dPAG).
DA hydrochloride suspended in a viscous castor oil gel (1 or 2 mg/kg) was applied (IN-DA) in a volume of 5 μL into the nostrils of adult Wistar male rats in order to evaluate its effects on (a) freezing induced by electric shock to the foot and (b) thresholds of freezing and escape and duration of post-stimulation freezing induced by electrical stimulation of the dPAG.
IN-DA attenuated freezing induced by electric shock to the foot in the three test trials, indicating that it reduced long-term fear responses. IN-DA also increased the threshold of dPAG stimulation-induced escape responses and reduced post-stimulation freezing.
IN-DA, which has previously been shown to facilitate learning and to have antidepressive-like effects, attenuated unconditioned fear responses elicited by peripheral and intramesencephalic (dPAG) stimulation and reduced long-term conditioned fear responses.
经鼻内给予多巴胺（IN-DA）可能通过鼻脑途径到达大脑，绕过血脑屏障，已被发现可增加细胞外 DA 并与纹状体中的 DA2 转运体结合。最近的研究表明，DA 在处理有信号和无条件的厌恶刺激方面起着重要作用，包括可能减轻对疼痛输入的反应的证据。本研究的目的是检查 IN-DA 对足底电击或背侧导水管周围灰质（dPAG）电刺激引起的与恐惧相关的行为的影响。
将盐酸多巴胺悬浮在粘性蓖麻油凝胶中（1 或 2 mg/kg），以 5 μL 的体积应用于成年 Wistar 雄性大鼠的鼻腔，以评估其对（a）足底电击引起的冻结和（b）dPAG 电刺激引起的冻结和逃避阈值以及刺激后冻结持续时间的影响。
IN-DA 减轻了足底电击引起的三个测试试验中的冻结，表明它减少了长期的恐惧反应。IN-DA 还增加了 dPAG 刺激诱导的逃避反应的阈值，并减少了刺激后的冻结。
先前已显示 IN-DA 促进学习并具有抗抑郁样作用，可减轻外周和中脑内（dPAG）刺激引起的非条件恐惧反应，并减少长期条件恐惧反应。
