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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Nefazodone in the rat: mimicry and antagonism of (-)-DOM-induced stimulus control.
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Nefazodone in the rat: mimicry and antagonism of (-)-DOM-induced stimulus control.

机译：大鼠中的奈法唑酮：（-）-DOM诱导的刺激控制的模仿和拮抗作用。

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摘要

Nefazodone is presently marketed as an antidepressant that inhibits both serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine reuptake while antagonizing pirenpirone (5-HT(2)) receptors. This 5-HT receptor type is believed to play a prominent role in the underlying mechanism of action of serotonergic hallucinogens. Antidepressant medications now represent the most commonly prescribed psychoactive medications in the world and are likely to be ingested in the presence of hallucinogens with increased frequency; the consequences are largely unknown. The present investigation examined the interaction between the serotonergic phenethylamine hallucinogen [-]-2,5-dimethoxy-4-methylamphetamine ([-]-DOM), and nefazodone, in rats trained with [-]-DOM [0.6 mg/kg; 75 min pretreatment time] as a discriminative stimulus. The data indicate that maximal substitution of nefazodone for the [-]-DOM stimulus was present using a 45-min pretreatment time before testing. Using this pretreatment time, a dose of nefazodone of 12.0 mg/kg administered alone resulted in 76% DOM-appropriate responding. When a range of doses of nefazodone was combined with the training dose of [-]-DOM, a pattern of responding compatible with partial agonism was observed. The intermediate degree of [-]-DOM generalization to nefazodone was significantly antagonized by the 5-HT antagonists, 5-HT(2), SR 46349B (5HT(2A/2C)), and M100907 (5-HT(2A)). Taken together, the present data suggest that (a) nefazodone acts as a partial agonist and (b) these effects are mediated by the 5-HT(2A) receptor.
机译：奈法唑酮目前作为抗抑郁药上市，既能抑制5-羟色胺（5-羟色胺，5-HT）和去甲肾上腺素的再摄取，又能拮抗哌仑皮酮（5-HT（2））受体。据信这种5-HT受体类型在血清素能致幻剂的潜在作用机理中起重要作用。现在，抗抑郁药物代表了世界上最常用的精神药物，并且可能在致幻剂存在的情况下以增加的频率被摄入;结果很大程度上未知。本研究调查了在接受[-]-DOM [0.6 mg / kg]训练的大鼠中，血清素能的苯乙胺致幻剂[-]-2,5-二甲氧基-4-甲基苯丙胺（[-]-DOM）与奈法唑酮之间的相互作用。 75分钟的预处理时间]作为判别刺激。数据表明，在测试前，经过45分钟的预处理时间，奈法唑酮最大程度地替代了[-]-DOM刺激。使用该预处理时间，单独服用12.0 mg / kg的奈法唑酮剂量可产生76％的DOM适当应答。当将一定剂量的奈法唑酮与训练剂量的[-]-DOM结合使用时，观察到与部分激动剂相容的反应模式。 5-HT拮抗剂，5-HT（2），SR 46349B（5HT（2A / 2C））和M100907（5-HT（2A））明显拮抗[-]-DOM泛滥至奈法唑酮的中等程度。两者合计，本数据表明（a）奈法唑酮起部分激动剂的作用，（b）这些作用是由5-HT（2A）受体介导的。

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