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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Effects of preexposure to dexfenfluramine, phentermine, dexfenfluramine-phentermine, or fluoxetine on sibutramine-induced hypophagia in the adult rat.
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Effects of preexposure to dexfenfluramine, phentermine, dexfenfluramine-phentermine, or fluoxetine on sibutramine-induced hypophagia in the adult rat.

机译：预暴露右芬氟拉明，芬特明，右芬氟拉明-芬特明或氟西汀对成年大鼠西布曲明诱发的吞咽的影响。

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摘要

The antiobesity drug sibutramine suppresses food intake via inhibition of reuptake of both norepinephrine (NE) and serotonin (5-HT) into brain terminals. The present study examined whether preexposure to other antiobesity drugs (fluoxetine [FLUOX], phentermine [PHEN], and dexfenfluramine [DEX]) that alter noradrenergic and/or serotonergic activity in brain induces tolerance or sensitization to the subsequent hypophagic action of sibutramine. Accordingly, adult male rats were treated (administered orally once per day for 21 days) with DEX (0, 1, or 3 mg/kg) and/or PHEN (0, 5, or 10 mg/kg), alone and in combination, or with the selective 5-HT reuptake inhibitor FLUOX (0, 15, or 30 mg/kg). Daily administration of PHEN persistently reduced food intake and body weight whereas tolerance developed to the hypophagic action of DEX or of FLUOX within the first week of daily administration. Moreover, low doses of DEX (1 mg/kg) and PHEN (5 mg/kg) interacted in a supra-additive manner to inhibit food intake and water intake and decrease body weight over the 21-day exposure period. After a recovery period of 9 days, a series of food intake trials were conducted to assess the hypophagic action of sibutramine (0, 1, 3, and 9 mg/kg po). Preexposure to PHEN (5 or 10 mg/kg), DEX (3 mg/kg), or FLUOX (30 mg/kg) resulted in a significant attenuation of the hypophagia induced by sibutramine over an 8-h, but not a 2-h, testing period. The pattern of cross-tolerance noted in this study is consistent with the observation that sibutramine inhibits eating via an interaction with noradrenergic and serotonergic mechanisms. Whether PHEN and DEX preexposure in humans alters subsequent sibutramine effectiveness is unknown.
机译：抗肥胖药西布曲明通过抑制去甲肾上腺素（NE）和5-羟色胺（5-HT）再进入脑末梢来抑制食物摄入。本研究检查了预暴露于其他抗肥胖药（氟西汀[FLUOX]，芬特明[PHEN]和右芬氟拉明[DEX]）是否会改变大脑中的去甲肾上腺素能和/或血清素能活性，从而诱导对随后的西布曲明低敏作用的耐受性或敏化性。因此，成年雄性大鼠单独或联合用DEX（0、1或3mg / kg）和/或PHEN（0、5或10mg / kg）治疗（每天口服一次，共21天）。 ，或使用选择性5-HT再摄取抑制剂FLUOX（0、15或30 mg / kg）。每天服用PHEN会持续减少食物摄入量和体重，而在每天服用第一周内，对DEX或FLUOX的低吞噬作用产生了耐受性。此外，低剂量的DEX（1 mg / kg）和PHEN（5 mg / kg）以超加性方式相互作用，从而在21天的暴露时间内抑制食物摄入和水分摄入并减轻体重。恢复期9天后，进行了一系列食物摄入试验，以评估西布曲明（0、1、3和9 m​​g / kg po）的抗吞咽作用。预先暴露于PHEN（5或10 mg / kg），DEX（3 mg / kg）或FLUOX（30 mg / kg）会导致西布曲明在8小时内显着减弱吞咽障碍，但2- h，测试期。这项研究中指出的交叉耐受模式与西布曲明通过与去甲肾上腺素能和血清素能机制的相互作用抑制进食的观察结果一致。尚不清楚人体内PHEN和DEX的预暴露是否会改变随后的西布曲明有效性。

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