Department of Pharmacology, University of São Paulo, São Paulo, Brazil.
J Psychopharmacol. 2020 Apr;34(4):391-399. doi: 10.1177/0269881119882797. Epub 2019 Oct 22.
Stimulation of serotonergic neurons within the dorsal raphe dorsomedial subnucleus facilitates inhibitory avoidance acquisition in the elevated T-maze. It has been hypothesized that such anxiogenic effect is due to serotonin release in the basolateral nucleus of the amygdala, where facilitation of serotonin 2C receptor-mediated neurotransmission increases anxiety. Besides the dorsal raphe dorsomedial subnucleus, the dorsal raphe caudal subnucleus is recruited by anxiogenic stimulus/situations. However, the behavioral consequences of pharmacological manipulation of this subnucleus are still unknown.
Investigate whether blockade of serotonin 2C receptors in the basolateral nucleus of the amygdala counteracts the anxiogenic effect caused by the stimulation of dorsal raphe dorsomedial subnucleus serotonergic neurons. Evaluate the effects caused by the excitatory amino acid kainic acid or serotonin 1A receptor-modulating drugs in the dorsal raphe caudal subnucleus.
Male Wistar rats were tested in the elevated T-maze and light-dark transition tests after intra-basolateral nucleus of the amygdala injection of the serotonin 2C receptor antagonist SB-242084 (6-chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxyamide dihydrochloride) followed by intra-dorsal raphe dorsomedial subnucleus administration of the serotonin 1A receptor antagonist WAY-100635 (N-[2-[4-2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinil-cyclohexanecarboxamide maleate). In the dorsal raphe caudal subnucleus, animals were injected with kainic acid, WAY-100635 or the serotonin 1A receptor agonist 8-OH-DPAT ((±)-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide) and tested in the elevated T-maze.
SB-242084 in the basolateral nucleus of the amygdala blocked the anxiogenic effect caused by the injection of WAY-100635 in the dorsal raphe dorsomedial subnucleus. Kainic acid in the dorsal raphe caudal subnucleus increased anxiety, but also impaired escape expression in the elevated T-maze. Neither WAY-100635 nor 8-OH-DPAT in the dorsal raphe caudal subnucleus affected rat's behavior in the elevated T-maze.
Serotonin 2C receptors in the basolateral nucleus of the amygdala mediate the anxiogenic effect caused by the stimulation of serotonergic neurons in the dorsal raphe dorsomedial subnucleus. The dorsal raphe caudal subnucleus regulates anxiety- and panic-like behaviors, presumably by a serotonin 1A receptor-independent mechanism.
刺激中缝背核背侧中缝亚核内的 5-羟色胺能神经元可促进高架 T 迷宫中的抑制性回避获得。据推测，这种焦虑效应是由于 5-羟色胺在杏仁核基底外侧核中的释放所致，其中 5-羟色胺 2C 受体介导的神经传递的促进增加了焦虑。除了中缝背核背侧中缝亚核外，背侧中缝尾侧亚核还被焦虑刺激/情况募集。然而，该亚核的药理学操作的行为后果仍然未知。
研究杏仁核基底外侧核中 5-羟色胺 2C 受体阻断是否可以抵消中缝背核背侧中缝亚核 5-羟色胺能神经元刺激引起的焦虑效应。评估兴奋性氨基酸海人酸或 5-羟色胺 1A 受体调节药物在背侧中缝尾侧亚核中的作用。
雄性 Wistar 大鼠在杏仁核基底外侧核内注射 5-羟色胺 2C 受体拮抗剂 SB-242084（6-氯-2,3-二氢-5-甲基-N-[[6-（2-甲基-3-吡啶基）氧基]-3-吡啶基]-1H-吲哚-1-羧酰胺二盐酸盐）后，在高架 T 迷宫和明暗过渡测试中进行测试，然后在中缝背核背侧中缝亚核内给予 5-羟色胺 1A 受体拮抗剂 WAY-100635（N-[2-[4-2-甲氧基苯基）-1-哌嗪基]乙基]-N-2-吡啶基-环己烷甲酰胺马来酸盐）。在背侧中缝尾侧亚核中，动物被注射海人酸、WAY-100635 或 5-羟色胺 1A 受体激动剂 8-OH-DPAT（（±）-8-羟基-2-（二正丙基氨基）四氢萘盐酸盐），并在高架 T 迷宫中进行测试。
杏仁核基底外侧核中的 SB-242084 阻断了 WAY-100635 在中缝背核背侧中缝亚核内注射引起的焦虑效应。背侧中缝尾侧亚核中的海人酸增加了焦虑，但也损害了高架 T 迷宫中的逃避表达。背侧中缝尾侧亚核中的 WAY-100635 或 8-OH-DPAT 均未影响大鼠在高架 T 迷宫中的行为。
杏仁核基底外侧核中的 5-羟色胺 2C 受体介导了中缝背核背侧中缝亚核内 5-羟色胺能神经元刺激引起的焦虑效应。背侧中缝尾侧亚核通过一种可能不依赖 5-羟色胺 1A 受体的机制调节焦虑和惊恐样行为。
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