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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Role of 5-HT1A receptors in the effects of acute chronic fluoxetine on extracellular serotonin in the frontal cortex.
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Role of 5-HT1A receptors in the effects of acute chronic fluoxetine on extracellular serotonin in the frontal cortex.

机译：5-HT1A受体在急性慢性氟西汀对额皮质中细胞外5-羟色胺的影响中的作用。

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Fluoxetine 10 mg/kg i.p. significantly increased the extracellular concentrations of serotonin (5-HT) in the frontal cortex as assessed by in vivo microdialysis. This effect was significantly potentiated when 0.3 mg/kg s.c. WAY-100635, a 5-HT1A receptor antagonist, was administered 30 min before. WAY-100635 by itself had no effect on extracellular 5-HT. Twenty-four hours after chronic fluoxetine schedule (10 mg/kg/day i.p. x 14 days), basal extracellular 5-HT concentrations in the frontal cortex were higher than those of animals that had received the vehicle chronically. At 24 h after the last dose, a challenge dose of fluoxetine (10 mg/kg i.p.) raised extracellular 5-HT similarly in chronically vehicle or fluoxetine treated rats. At this same interval 25 micrograms/kg s.c. 8-OH-DPAT, a 5-HT1A receptor agonist, significantly reduced extracellular 5-HT only in the frontal cortex of rats treated chronically with the vehicle. Examining basal extracellular 5-HT, the effect of a challenge dose of fluoxetineand the effect of 25 micrograms/kg 8-OH-DPAT after 96 h washout, no differences were found between chronically fluoxetine and vehicle-treated rats. The results confirm that the ability of fluoxetine to stimulate 5-HT1A autoreceptors through an increase of endogenous 5-HT attenuates its effect on cortical dialysate 5-HT. Chronic fluoxetine increased the basal concentrations of extracellular 5-HT only when a substantial amount of its metabolite was present in the brain and during the desensitization of presynaptic 5-HT1A autoreceptors (24 h after the last dose). These effects, in fact, disappeared after 96 h washout. The continuous presence of the drug may, therefore, be necessary to maintain extracellular 5-HT at concentrations high enough to produce a therapeutic effect.
机译：氟西汀10 mg / kg腹腔注射通过体内微透析评估，显着增加了额叶皮质中5-羟色胺（5-HT）的细胞外浓度。当剂量为0.3 mg / kg s.c时，这种作用明显增强。 5-HT1A受体拮抗剂WAY-100635在服用前30分钟服用。 WAY-100635本身对细胞外5-HT无影响。慢性氟西汀时间表（10 mg / kg /天，腹腔内注射x 14天）后二十四小时，额叶皮层的基础细胞外5-HT浓度高于长期接受该载体的动物。在最后一次给药后24小时，氟西汀的激发剂量（10mg / kg i.p.）在慢性媒介物或氟西汀治疗的大鼠中类似地升高了细胞外5-HT。在相同的间隔25微克/千克s.c. 8-OH-DPAT是一种5-HT1A受体激动剂，仅在长期接受该媒介物治疗的大鼠额叶皮质中才能显着降低细胞外5-HT。在冲洗96小时后，检查了基础细胞外5-HT，氟西汀激发剂量的作用和25微克/千克8-OH-DPAT的作用，在慢性氟西汀和媒介物处理的大鼠之间未发现差异。结果证实，氟西汀通过增加内源性5-HT刺激5-HT1A自身受体的能力减弱了其对皮质透析液5-HT的作用。慢性氟西汀只有在大脑中存在大量代谢物且在突触前5-HT1A自身受体脱敏期间（最后一次给药后24小时），才增加细胞外5-HT的基础浓度。实际上，这些效果在96小时冲洗后消失了。因此，可能需要药物的连续存在以将细胞外5-HT维持在足够高的浓度以产生治疗效果。

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