Pesarico Ana Paula, Sampaio Tuane Bazanella, Stangherlin Eluza Curte, Mantovani Anderson C, Zeni Gilson, Nogueira Cristina Wayne
Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, CEP 97105-900, Santa Maria, Rio Grande do Sul, Brasil.
Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, CEP 97105-900, Santa Maria, Rio Grande do Sul, Brasil.
Prog Neuropsychopharmacol Biol Psychiatry. 2014 Oct 3;54:179-86. doi: 10.1016/j.pnpbp.2014.06.001. Epub 2014 Jun 14.
The aim of the present study was to investigate the role of monoaminergic system in the antidepressant-like action of 7-fluoro-1,3-diphenylisoquinoline-1-amine (FDPI), a derivative of isoquinoline class, in Swiss mice. The antidepressant-like effect of FDPI was characterized in the modified forced swimming test (FST) and the possible mechanism of action was investigated by using serotonergic, dopaminergic and noradrenergic antagonists. Monoamine oxidase (MAO) activity and [(3)H]serotonin (5-HT) uptake were determined in prefrontal cortices of mice. The results showed that FDPI (1, 10 and 20mg/kg, i.g.) reduced the immobility time and increased the swimming time but did not alter climbing time in the modified FST. These effects were similar to those of paroxetine (8mg/kg, i.p.), a positive control. Pretreatments with p-chlorophenylalanine (100mg/kg, i.p., an inhibitor of 5-HT synthesis), WAY100635 (0.1mg/kg, s.c., 5-HT1A antagonist), ondansetron (1mg/kg, i.p., a 5-HT3 receptor antagonist), haloperidol (0.2mg/kg, i.p., a non-selective D2 receptor antagonist) and SCH23390 (0.05mg/kg, s.c., a D1 receptor antagonist) were effective to block the antidepressant-like effect of FDPI at a dose of 1mg/kg in the FST. Ritanserin (1mg/kg, i.p., a 5-HT2A/2C receptor antagonist), sulpiride (50mg/kg, i.p., a D2 and D3 receptor antagonist), prazosin (1mg/kg, i.p., an α1 receptor antagonist), yohimbine (1mg/kg, i.p., an α2 receptor antagonist) and propranolol (2mg/kg, i.p., a β receptor antagonist) did not modify the effect of FDPI in the FST. FDPI did not change synaptosomal [(3)H]5-HT uptake. At doses of 10 and 20mg/kg FDPI inhibited MAO-A and MAO-B activities. These results suggest that antidepressant-like effect of FDPI is mediated mostly by serotonergic and dopaminergic systems.
本研究的目的是探讨单胺能系统在异喹啉类衍生物7-氟-1,3-二苯基异喹啉-1-胺（FDPI）对瑞士小鼠的抗抑郁样作用中的作用。通过改良强迫游泳试验（FST）对FDPI的抗抑郁样作用进行表征，并使用5-羟色胺能、多巴胺能和去甲肾上腺素能拮抗剂研究其可能的作用机制。测定小鼠前额叶皮质中的单胺氧化酶（MAO）活性和[³H]5-羟色胺（5-HT）摄取量。结果显示，FDPI（1、10和20mg/kg，灌胃）在改良FST中减少了不动时间并增加了游泳时间，但未改变攀爬时间。这些作用与阳性对照帕罗西汀（8mg/kg，腹腔注射）相似。用对氯苯丙氨酸（100mg/kg，腹腔注射，一种5-HT合成抑制剂）、WAY100635（0.1mg/kg，皮下注射，5-HT1A拮抗剂）、昂丹司琼（1mg/kg，腹腔注射，一种5-HT3受体拮抗剂）、氟哌啶醇（0.2mg/kg，腹腔注射，一种非选择性D2受体拮抗剂）和SCH23390（0.05mg/kg，皮下注射，一种D1受体拮抗剂）预处理可有效阻断FDPI在FST中1mg/kg剂量时的抗抑郁样作用。利坦色林（1mg/kg，腹腔注射，一种5-HT2A/2C受体拮抗剂）、舒必利（50mg/kg，腹腔注射，一种D2和D3受体拮抗剂）、哌唑嗪（1mg/kg，腹腔注射，一种α1受体拮抗剂）、育亨宾（1mg/kg，腹腔注射，一种α2受体拮抗剂）和普萘洛尔（2mg/kg，腹腔注射，一种β受体拮抗剂）未改变FDPI在FST中的作用。FDPI未改变突触体[³H]5-HT摄取。在10和20mg/kg剂量下，FDPI抑制MAO-A和MAO-B活性。这些结果表明，FDPI的抗抑郁样作用主要由5-羟色胺能和多巴胺能系统介导。
