血清素受体亚型参与胍丁胺在小鼠强迫游泳试验中抗抑郁样效应的证据。
Evidence for serotonin receptor subtypes involvement in agmatine antidepressant like-effect in the mouse forced swimming test.
作者信息
Dias Elpo Zomkowski Andréa, Oscar Rosa Angelo, Lin Jaime, Santos Adair R S, Calixto João Batista, Lúcia Severo Rodrigues Ana
机构信息
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis 88040-900, SC, Brazil.
出版信息
Brain Res. 2004 Oct 15;1023(2):253-63. doi: 10.1016/j.brainres.2004.07.041.
This study investigated the involvement of 5-HT(1) and 5-HT(2) receptors in the antidepressant-like effect of agmatine in the mouse forced swimming test (FST). Pretreatment with p-chlorophenylalanine methyl ester (PCPA; 100 mg/kg, intraperitoneally (i.p.), an inhibitor of serotonin synthesis, for 4 consecutive days), methysergide (5 mg/kg, i.p., a serotonin (5-HT) antagonist), pindolol (32 mg/kg, i.p., a 5-HT(1A/1B) receptor/beta-adrenoceptor antagonist), N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridynyl)cyclohexanecarboxamide (WAY 100635; 0.3 mg/kg, subcutaneously (s.c.), a selective 5-HT(1A) receptor antagonist), 1-(2-methoxyphenyl)-4[-(2-phthalimido)butyl]piperazine) (NAN-190; 0.5 mg/kg, i.p., a 5-HT(1A) receptor antagonist), 1-(2-(1-pyrrolyl)-phenoxy)-3-isopropylamino-2-propanol (isamoltane; 2.5 mg/kg, i.p., a 5-HT(1B) receptor antagonist), cyproheptadine (3 mg/kg, i.p., a 5-HT(2) antagonist) or ketanserin (5 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist), but not with propranolol (2 mg/kg, i.p., a beta-adrenoceptor antagonist), prevented the effect of agmatine (10 mg/kg, i.p.) in the FST. A subeffective dose of agmatine (0.001 mg/kg, i.p.) produced a synergistic antidepressant-like effect with pindolol (32 mg/kg), NAN-190 (0.5 mg/kg, i.p.), WAY 100635 (0.03 mg/kg, s.c.), (+)-8-hydroxy-2-(di-n-propylamino)tetralin HBr (8-OH-DPAT; 0.01 mg/kg, i.p., a 5-HT(1A) receptor agonist), R(-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI; 1 mg/kg, i.p., a preferential 5-HT(2A) receptor agonist), or fluoxetine (10 mg/kg, i.p., a selective serotonin reuptake inhibitor, SSRI) but not with isamoltane (2.5 mg/kg, i.p.), ritanserin (4 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist) or ketanserin (5 mg/kg, i.p.). Taken together, the results firstly demonstrate that agmatine antidepressant-like effects in the FST seem to be mediated, at least in part, by an interaction with 5-HT(1A/1B) and 5-HT(2) receptors.
本研究在小鼠强迫游泳试验（FST）中探究了5-羟色胺（5-HT）1型和2型受体在胍丁胺抗抑郁样效应中的作用。连续4天腹腔注射（i.p.）对氯苯丙氨酸甲酯（PCPA；100 mg/kg，血清素合成抑制剂）、麦角酰二乙胺（5 mg/kg，i.p.，一种血清素（5-HT）拮抗剂）、吲哚洛尔（32 mg/kg，i.p.，一种5-HT1A/1B受体/β-肾上腺素能受体拮抗剂）、N-[2-[4-(2-甲氧基苯基)-1-哌嗪基]乙基]-N-(2-吡啶基)环己烷甲酰胺（WAY 100635；0.3 mg/kg，皮下注射（s.c.），一种选择性5-HT1A受体拮抗剂）、1-(2-甲氧基苯基)-4[-(2-邻苯二甲酰亚胺基)丁基]哌嗪（NAN-190；0.5 mg/kg，i.p.，一种5-HT1A受体拮抗剂）、1-(2-(1-吡咯基)-苯氧基)-3-异丙基氨基-2-丙醇（异美汀；2.5 mg/kg，i.p.，一种5-HT1B受体拮抗剂）、赛庚啶（3 mg/kg，i.p.，一种5-HT2拮抗剂）或酮色林（5 mg/kg，i.p.，一种5-HT2A/2C受体拮抗剂）进行预处理，但不包括普萘洛尔（2 mg/kg，i.p.，一种β-肾上腺素能受体拮抗剂），可预防胍丁胺（10 mg/kg，i.p.）在FST中的效应。亚有效剂量的胍丁胺（0.001 mg/kg，i.p.）与吲哚洛尔（32 mg/kg）、NAN-190（0.5 mg/kg，i.p.）、WAY 100635（0.03 mg/kg，s.c.）、（+）-8-羟基-2-（二正丙基氨基）四氢化萘溴化物（8-OH-DPAT；0.01 mg/kg，i.p.，一种5-HT1A受体激动剂）、R（-）-1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷盐酸盐（DOI；1 mg/kg，i.p.，一种优先的5-HT2A受体激动剂）或氟西汀（10 mg/kg，i.p.，一种选择性血清素再摄取抑制剂，SSRI）产生协同抗抑郁样效应，但与异美汀（2.5 mg/kg，i.p.）、利坦色林（4 mg/kg，i.p.，一种5-HT2A/2C受体拮抗剂）或酮色林（5 mg/kg，i.p.）不产生协同效应。综上所述，结果首先表明胍丁胺在FST中的抗抑郁样效应似乎至少部分是通过与5-HT1A/1B和5-HT2受体相互作用介导的。
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