Redrobe J P, Bourin M, Colombel M C, Baker G B
GIS Médicament, JE 2027 Neurobiologie de l'anxieté, Faculté de Médecine, Nantes, France.
J Psychopharmacol. 1998;12(4):348-55. doi: 10.1177/026988119801200404.
The present study was designed to evaluate the psychopharmacological profile of the selective serotonin reuptake inhibitor paroxetine, and thus assess potential noradrenergic and/or serotonergic activity. Paroxetine dose-dependently increased mobility time in the mouse forced swimming test (8, 16, 32 and 64 mg/kg, i.p.) and reduced spontaneous locomotor activity when administered at a high dose (64 mg/kg, i.p.). Prior administration of 8-hydroxy-2-(di-n-propylamino)tetralin (1 mg/kg, i.p.), (+/-) pindolol (32 mg/kg, i.p.) or 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridyl)-1H-indole (RU 24969) (1 mg/kg, i.p.) potentiated the antidepressant-like effects of subactive doses of paroxetine (1, 2 and 4 mg/kg, i.p.) in the mouse forced swimming test. These effects were antagonized by prior administration of 1-(2-methoxyphenyl)-4-[-(2-phthalimido)butyl]piperazine) (0.5 mg/kg, i.p.). Complementary studies suggested that RU24969-induced anti-immobility effects were a result of an increase in locomotor activity; other interactions were without increase/decrease in locomotor activity. Acute administration of paroxetine (8, 16, and 32 mg/kg, i.p.) antagonized the hypothermia induced by the D2/D1 receptor agonist, apomorphine (16 mg/kg, s.c.), while repeated treatment with paroxetine (32 mg/kg) attenuated clonidine-induced (0.5 mg/kg, i.p.) hypothermia. Pre-treatment with the serotonergic neurotoxin, para-chlorophenylalanine attenuated the anti-immobility effects of low doses of paroxetine (8 and 16 mg/kg, i.p.) in the forced swimming test, whereas a higher dose of paroxetine remained active (32 mg/kg, i.p.). The results of the present study indicated that paroxetine displayed both noradrenergic-like and serotonergic-like activity in the pre-clinical psychopharmacological tests employed.
本研究旨在评估选择性5-羟色胺再摄取抑制剂帕罗西汀的精神药理学特征，从而评估其潜在的去甲肾上腺素能和/或5-羟色胺能活性。帕罗西汀在小鼠强迫游泳试验中剂量依赖性地增加活动时间（腹腔注射8、16、32和64mg/kg），并在高剂量（腹腔注射64mg/kg）给药时减少自发运动活性。预先给予8-羟基-2-（二正丙基氨基）四氢萘（腹腔注射1mg/kg）、（±）吲哚洛尔（腹腔注射32mg/kg）或5-甲氧基-3-（1,2,3,6-四氢-4-吡啶基）-1H-吲哚（RU 24969）（腹腔注射1mg/kg）可增强亚有效剂量帕罗西汀（腹腔注射1、2和4mg/kg）在小鼠强迫游泳试验中的抗抑郁样作用。这些作用可被预先给予1-（2-甲氧基苯基）-4-[（2-邻苯二甲酰亚胺基）丁基]哌嗪（腹腔注射0.5mg/kg）所拮抗。补充研究表明，RU24969诱导的抗不动作用是运动活性增加的结果；其他相互作用未伴有运动活性的增加/减少。急性给予帕罗西汀（腹腔注射8、16和32mg/kg）可拮抗D2/D1受体激动剂阿扑吗啡（皮下注射16mg/kg）诱导的体温过低，而反复给予帕罗西汀（32mg/kg）可减弱可乐定（腹腔注射0.5mg/kg）诱导的体温过低。用5-羟色胺能神经毒素对氯苯丙氨酸预处理可减弱低剂量帕罗西汀（腹腔注射8和16mg/kg）在强迫游泳试验中的抗不动作用，而较高剂量的帕罗西汀（腹腔注射32mg/kg）仍有活性。本研究结果表明，在所用的临床前精神药理学试验中，帕罗西汀表现出去甲肾上腺素能样和5-羟色胺能样活性。
