Stimulus properties of fluvoxamine in a conditioned taste aversion procedure
Stimulus properties of fluvoxamine in a conditioned taste aversion procedure
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DOI：
10.1007/s002130050794
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发表时间：
1998-12-01
影响因子：
3.4
通讯作者：
Olivier, B
中科院分区：
文献类型：
--
作者：
Gommans, J;Bouwknecht, JA;Olivier, B
采用条件味觉厌恶（CTA）实验研究了血清素再摄取抑制剂（SSRIs）氟伏沙明和氟西汀对小鼠的刺激作用。氟伏沙明诱发了可靠的CTA (ED(50) = 24 mg/kg， SC)，许多药物作为暴露前药物进行了测试。预先暴露于5-羟色胺（5-HT）（1A）受体激动剂flesinoxan和+/—8-羟基-二丙基氨基四乙胺（8-OH-DPAT）可阻止氟伏沙明（50 mg/kg， SC）诱导的CTA。预暴露于5-HT（2C）受体激动剂MK 212[6-氯-2（1-哌嗪基）吡嗪]可部分预防氟伏沙明诱导的CTA，预暴露于5-HT（2A/2C）受体激动剂DOI[1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷HCl]不能预防氟伏沙明诱导的CTA。肉肉素预暴露对氟西汀（10 mg/kg， SC）诱导的味觉厌恶也有完全抑制作用。这与氟西汀先前获得的结果形成对比，氟西汀发现其刺激主要由5-HT（2C）介导，并在较小程度上由5-HT（1A）受体介导。因此，我们直接比较了两种SSRIs。预暴露于氟伏沙明可预防氟西汀诱导的CTA，而预暴露于氟西汀仅能部分预防氟伏沙明诱导的CTA。我们得出结论，5-HT（1A）受体参与了氟伏沙明和氟西汀的刺激特性，5-HT（2C）受体参与了氟伏沙明，特别是氟西汀，并且，主要基于交叉比较试验，两种SSRIs具有不同的刺激特性。
A conditioned taste aversion (CTA) procedure in mice was used to investigate the stimulus effects of the serotonin reuptake inhibitors (SSRIs) fluvoxamine and fluoxetine. Fluvoxamine elicited a reliable CTA (ED(50) = 24 mg/kg, SC) and a number of drugs were tested as pre-exposure drugs. Pre-exposure to the serotonin (5-HT)(1A) receptor agonists flesinoxan and +/--8-hydroxy-dipropylaminotetralin (8-OH-DPAT) prevented the CTA induced by fluvoxamine (50 mg/kg, SC). Pre-exposure with the 5-HT(2C) receptor agonist MK 212 [6-chloro-2(1-piperazinyl)pyrazine] partially prevented the fluvoxamine-induced CTA, pre-exposure with the 5-HT(2A/2C) receptor agonist DOI [1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl] did not prevent the CTA induced by fluvoxamine. Flesinoxan pre-exposure also prevented the taste aversion induced by fluoxetine (10 mg/kg, SC) completely. This contrasts previous results obtained with fluoxetine, where was found that its stimulus is primarily mediated by 5-HT(2C), and to a lesser degree by 5-HT(1A) receptors. Therefore, we compared the two SSRIs directly. Pre-exposure to fluvoxamine prevented the fluoxetine-induced CTA, whereas pre-exposure to fluoxetine only partially prevented the fluvoxamine-induced CTA. We conclude that 5-HT(1A) receptors are involved in the stimulus properties of both fluvoxamine and fluoxetine, that 5-HT(2C) receptors are involved in fluvoxamine and especially fluoxetine, and, based primarily on the cross-comparison tests, that the two SSRIs have somewhat different stimulus properties.