Non-selective α₂-adrenoreceptor (AR) stimulation delivers favourable sedative, analgesic, muscle relaxant and anxiolytic actions in companion animals, but is associated with cardiovascular and respiratory side effects. Anxiety conditions underscore monoamine disturbances amenable to α₂-AR modulation. We investigated sub-chronic (14 day s.c.) treatment with the selective α_2C-AR antagonist, ORM-10921 (0.03, 0.1, 0.3 mg/kg/d) on hippocampal noradrenaline (NA), dopamine (DA), serotonin (5-HT) and their turnover levels in stress sensitive Flinders Sensitive Line (FSL) rats versus Flinders Resistant Line (FRL) controls, using high performance liquid chromatography. The effects of ORM-10921 were compared to the non-selective α₂-AR antagonist, idazoxan (IDAZ; 3 mg/kg/d), and to imipramine (IMI; 15 mg/kg/d), a reference antidepressant in this model. FSL rats displayed significantly reduced 5-HT (p = 0.03) and DA (p = 0.02) levels vs. FRL controls, while NA levels showed a similar trend. ORM-10921 significantly increased NA (all doses p ≤ 0.02), 5-HT (0.1 and 0.3 mg/kg p ≤ 0.03) and DA levels (all doses p ≤ 0.03), which correlated with decreased monoamine turnover. In contrast, IDAZ significantly elevated NA (p < 0.005) and DA (p < 0.004) but not 5-HT levels. IMI also significantly increased 5-HT (p < 0.009), with a tendency to increase NA (p = 0.09) but not DA. ORM-10921 exerts similar albeit broader effects on hippocampal monoamines than IDAZ, explaining earlier established efficacy associated with α_2C-AR antagonism in animal models of depression and cognitive dysfunction. These and the current studies encourage application of ORM-10921 in depression in humans, as well as raise the intriguing possibility that selective α_2C-AR antagonists may be beneficial in anxiety and stress-related disorders in companion animals. Both warrant further study.

非选择性α ₂肾上腺素受体（AR）的刺激提供有利镇静，止痛，肌肉松弛和伴侣动物抗焦虑的动作，但与心血管和呼吸系统的副作用相关联。焦虑条件下划线单胺干扰服从α ₂ -AR调制。我们研究了与亚慢性（第14天皮下）治疗所述选择性α _2C -AR拮抗剂，ORM-10921（0.03，0.1，0.3毫克/千克/ d）对海马去甲肾上腺素（NA），多巴胺（DA），血清素（5-使用高效液相色谱法，对应激敏感的弗林德斯敏感谱系（FSL）大鼠和弗林德斯抗性谱系（FRL）对照中的（-HT）及其更新水平。ORM-10921的效果进行了比较，非选择性α ₂-AR拮抗剂伊达唑烷（IDAZ; 3 mg / kg / d）和丙咪嗪（IMI; 15 mg / kg / d），该模型中的参考抗抑郁药。 与FRL对照组相比，FSL大鼠的5-HT（p  = 0.03）和DA（p = 0.02）水平显着降低，而NA水平则显示出相似的趋势。ORM-10921显著增加NA（所有剂量p  ≤0.02），5-HT（0.1和0.3mg / kg的p  ≤0.03）和DA水平（所有剂量P≤0.03），这与减少的单胺周转相关。相反，IDAZ显着提高了NA（p  <0.005）和DA（p  <0.004），但没有提高5-HT水平。IMI还显着增加了5-HT（p  <0.009），并具有增加NA（p = 0.09），而不是DA。ORM-10921施加虽然对海马的单胺比IDAZ更广泛的作用类似，说明采用α相关成立时间较早的功效_2C -AR拮抗抑郁和认知功能障碍的动物模型。这和目前的研究鼓励抑郁ORM-10921的应用在人类，以及提高了有趣的可能性，选择性α _2C -AR拮抗剂可以在伴侣动物焦虑和压力有关的疾病有益。两者都需要进一步研究。