Kõks S, Beljajev S, Koovit I, Abramov U, Bourin M, Vasar E
Department of Physiology, University of Tartu, Estonia.
Psychopharmacology (Berl). 2001 Jan;153(3):365-72. doi: 10.1007/s002130000594.
To investigate whether a 5-hydroxytryptamine (5-HT) reuptake inhibitor (paroxetine) has an anxiogenic-like effect and what possible pharmacological mechanism underlies that action.
We used the rat elevated plus-maze paradigm followed by measurement of locomotor activity. Some of the rats were subjected to handling and adaptation to the experimental situation, while the rest were naive to the test situation. Paroxetine was administered as a single treatment and in combination with the 5-HT1A receptor agonist (8-OH-DPAT) or 5-HT2A/2C receptor antagonist (deramciclane).
The administration of paroxetine induced an anxiogenic-like action in rats adapted to handling, but not in handling naive animals. Treatment with paroxetine (0.1-2 mg/kg) reduced the number of open arm visits and time spent in open arms, and the ratio between open and total arm entries in the elevated plus-maze. Paroxetine also decreased the number of line crossings and head-dips. Paroxetine caused the strongest anti-exploratory action at a dose of 0.5 mg/kg. Paroxetine did not suppress the locomotor activity of rats, showing that the described anti-exploratory effect was behaviourally specific to the plus-maze. Pretreatment with 8-OH-DPAT (0.05 mg/kg) completely reversed the anxiogenic-like action of paroxetine, whereas treatment with deramciclane (2 mg/kg) affected only the number of closed arm visits. Deramciclane (0.5-2 mg/kg) and 8-OH-DPAT (0.01-0.1 mg/kg) changed neither exploratory behaviour nor locomotor activity if given as single treatments to the habituated rats.
The 5-HT reuptake inhibitor, paroxetine, at a low dose (0.5 mg/kg) induces an anxiogenic-like action in handling adapted rats. The effectiveness of 8-OH-DPAT against paroxetine probably supports a role of both pre- and postsynaptic 5HT-ergic mechanisms in the anxiogenic-like action of paroxetine.
研究5-羟色胺（5-HT）再摄取抑制剂（帕罗西汀）是否具有类焦虑作用以及该作用潜在的药理学机制。
我们采用大鼠高架十字迷宫范式，随后测量运动活性。部分大鼠接受了实验操作及环境适应，而其余大鼠对测试环境陌生。帕罗西汀单独给药，并与5-HT1A受体激动剂（8-OH-DPAT）或5-HT2A/2C受体拮抗剂（地拉环素）联合给药。
帕罗西汀给药在适应实验操作的大鼠中诱发了类焦虑作用，但在未适应实验操作的动物中未出现。帕罗西汀（0.1 - 2mg/kg）治疗减少了高架十字迷宫中进入开放臂的次数、在开放臂停留的时间以及开放臂与总臂进入次数的比值。帕罗西汀还减少了穿行次数和探首次数。帕罗西汀在0.5mg/kg剂量时产生最强的抗探索作用。帕罗西汀未抑制大鼠的运动活性，表明所描述的抗探索作用在行为上对十字迷宫具有特异性。8-OH-DPAT（0.05mg/kg）预处理完全逆转了帕罗西汀的类焦虑作用，而地拉环素（2mg/kg）治疗仅影响进入封闭臂的次数。地拉环素（0.5 - 2mg/kg）和8-OH-DPAT（0.01 - 0.1mg/kg）单独给适应环境的大鼠给药时，既不改变探索行为也不改变运动活性。
5-HT再摄取抑制剂帕罗西汀在低剂量（0.5mg/kg）时在适应实验操作的大鼠中诱发类焦虑作用。8-OH-DPAT对抗帕罗西汀的有效性可能支持突触前和突触后5-羟色胺能机制在帕罗西汀类焦虑作用中均发挥作用。
