Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
Department of Neurosciences and Behavior, Division of Psychiatry, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
J Psychopharmacol. 2020 Apr;34(4):383-390. doi: 10.1177/0269881120907960. Epub 2020 Feb 28.
Oxytocin (OT) has been widely linked to positive social interactions, and there is great interest in OT as a therapy for a variety of neuropsychiatric conditions. Recent evidence also suggests that OT can play an important role in the mediation of anxiety-associated defensive responses, including a role for serotonin (5-HT) neurotransmission in this action. However, it is presently unknown whether OT additionally regulates the expression of panic-related behaviors, such as escape, by acting in the dorsal periaqueductal gray (dPAG), a key panic-regulating area. This study aimed to investigate the consequence of OT injection in the dPAG on escape expression and whether facilitation of 5-HT neurotransmission in this midbrain area is implicated in this action.
Male Wistar rats were injected with OT in the dPAG and tested for escape expression in the elevated T-maze (ETM) and dPAG electrical stimulation tests. Using the latter test, OT's effect was also investigated after previous intra-dPAG injection of the OT receptor antagonist atosiban, the preferential antagonists of 5-HT and 5-HT receptors, WAY-100635 and ketanserin, respectively, or systemic pretreatment with the 5-HT synthesis inhibitor p-CPA.
OT impaired escape expression in the two tests used, suggesting a panicolytic-like effect. In the ETM, the peptide also facilitated inhibitory avoidance acquisition, indicating an anxiogenic effect. Previous administration of atosiban, WAY-100635, ketanserin, or p-CPA counteracted OT's anti-escape effect.
OT and 5-HT in the dPAG interact in the regulation of panic- and anxiety-related defensive responses. These findings open new perspectives for the development of novel therapeutic strategies for the treatment of anxiety disorders.
催产素（OT）与积极的社会互动广泛相关，并且人们对 OT 作为治疗各种神经精神疾病的治疗方法非常感兴趣。最近的证据还表明，OT 可以在介导焦虑相关的防御反应中发挥重要作用，包括 5-羟色胺（5-HT）神经递质在这种作用中的作用。然而，目前尚不清楚 OT 是否通过作用于背侧periaqueductal gray（dPAG）来调节与恐慌相关的行为（如逃避）的表达，dPAG 是调节恐慌的关键区域。本研究旨在研究 dPAG 中 OT 注射对逃避表达的影响，以及该中脑区域中 5-HT 神经传递的促进是否与此作用有关。
雄性 Wistar 大鼠在 dPAG 中注射 OT，然后在高架 T 迷宫（ETM）和 dPAG 电刺激测试中测试逃避表达。在后一种测试中，还研究了在 dPAG 内预先注射 OT 受体拮抗剂阿托西班、5-HT 和 5-HT 受体的选择性拮抗剂 WAY-100635 和酮色林，或全身预处理 5-HT 合成抑制剂 p-CPA 后，OT 的作用。
OT 削弱了两种测试中逃避的表达，表明具有类似惊恐的作用。在 ETM 中，该肽还促进了抑制性回避的获得，表明具有焦虑作用。先前给予阿托西班、WAY-100635、酮色林或 p-CPA 可抵消 OT 的抗逃避作用。
dPAG 中的 OT 和 5-HT 相互作用调节恐慌和焦虑相关的防御反应。这些发现为开发治疗焦虑障碍的新治疗策略开辟了新的前景。
