Bourin M, Redrobe J P, Baker G B
GIS Médicament, JE 2027 Neurobiologie de l'anxieté, Faculté de Médicine BP 53508, Nantes, France.
Psychopharmacology (Berl). 1998 Apr;136(3):226-34. doi: 10.1007/s002130050560.
The present study was undertaken to identify the receptor subtypes involved in (+/-) pindolol's ability to enhance the effects of antidepressant drugs in the mouse forced swimming test. Interaction studies were performed with S 15535 (presynaptic 5-HT1A receptor agonist) and methiothepin (5-HT1B autoreceptor antagonist) in an attempt to attenuate or potentiate antidepressant-like activity. (+/-) Pindolol was tested in combination with selective agonists and antagonists at 5-HT1, 5-HT2 and 5-HT3 receptor subtypes. Pretreatment with S 15535 and methiothepin attenuated the activity of paroxetine, fluvoxamine and citalopram (32 mg/kg, i.p.; P < 0.01). (+/-) Pindolol (32 mg/kg, i.p.) induced significant anti-immobility effects when tested in combination with 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridyl)-1H-indole (RU 24969) (1 mg/kg, i.p.; P < 0.05), 1-(2-methoxyphenyl)-4-[-(2-phthalimido) butyl]piperazine) (NAN 190) (0.5 mg/kg; P < 0.05) and ondansetron (0.00001 mg/kg, i.p.; P < 0.01). Pretreatment with NAN 190 (0.5 mg/kg, i.p.) potentiated the effects of RU 24969 (1 mg/kg, i.p.; P < 0.05) and (+/-) pindolol (32 mg/kg, i.p.; P < 0.05) in the forced swimming test, as did ondansetron (0.00001 mg/kg, i.p.). Significant additive effects were induced when RU 24969 (1 mg/kg, i.p.) was tested in combination with NAN 190 (0.5 mg/kg, i.p.; P < 0.05), (+/-) pindolol (32 mg/kg, i.p.; P < 0.05) and ondansetron (0.0000 mg/kg, i.p.; P < 0.05). 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (1 mg/kg, i.p.) or ketanserin (8 mg/kg, i.p.) did not induce significant antidepressant-like effects with any of the agonists/antagonists tested. The results of the present study suggest that pindolol is acting at presynaptic 5-HT1B serotonergic receptors, in addition to the 5-HT1A subtype, in augmenting the activity of antidepressants in the mouse forced swimming test.
本研究旨在确定在小鼠强迫游泳试验中，（±）吲哚洛尔增强抗抑郁药作用所涉及的受体亚型。用S 15535（突触前5-HT1A受体激动剂）和甲硫哒嗪（5-HT1B自身受体拮抗剂）进行相互作用研究，试图减弱或增强类抗抑郁活性。（±）吲哚洛尔与5-HT1、5-HT2和5-HT3受体亚型的选择性激动剂和拮抗剂联合进行测试。用S 15535和甲硫哒嗪预处理可减弱帕罗西汀、氟伏沙明和西酞普兰（32mg/kg，腹腔注射；P<0.01）的活性。（±）吲哚洛尔（32mg/kg，腹腔注射）与5-甲氧基-3-（1,2,3,6-四氢-4-吡啶基）-1H-吲哚（RU 24969）（1mg/kg，腹腔注射；P<0.05）、1-（2-甲氧基苯基）-4-[（2-邻苯二甲酰亚胺基）丁基]哌嗪（NAN 190）（0.5mg/kg；P<0.05）和昂丹司琼（0.00001mg/kg，腹腔注射；P<0.01）联合测试时，可诱导出显著的抗不动效应。用NAN 190（0.5mg/kg，腹腔注射）预处理可增强RU 24969（1mg/kg，腹腔注射；P<0.05）和（±）吲哚洛尔（32mg/kg，腹腔注射；P<0.05）在强迫游泳试验中的作用，昂丹司琼（0.00001mg/kg，腹腔注射）也有此作用。当RU 24969（1mg/kg，腹腔注射）与NAN 190（0.5mg/kg，腹腔注射；P<0.05）、（±）吲哚洛尔（32mg/kg，腹腔注射；P<0.05）和昂丹司琼（0.0000mg/kg，腹腔注射；P<0.05）联合测试时，可诱导出显著的相加效应。8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）（1mg/kg，腹腔注射）或酮色林（8mg/kg，腹腔注射）与所测试的任何激动剂/拮抗剂联合使用时，均未诱导出显著的类抗抑郁效应。本研究结果表明，在小鼠强迫游泳试验中，吲哚洛尔除作用于5-HT1A亚型外，还作用于突触前5-HT1B血清素能受体，从而增强抗抑郁药的活性。
