首页> 外文期刊>Pharmacology, Biochemistry and Behavior >The 5-HT3 receptor partial agonist MD-354 (meta-chlorophenylguanidine) enhances the discriminative stimulus actions of (+)amphetamine in rats.
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The 5-HT3 receptor partial agonist MD-354 (meta-chlorophenylguanidine) enhances the discriminative stimulus actions of (+)amphetamine in rats.

机译:5-HT3受体部分激动剂MD-354(间氯苯胍)增强大鼠中(+)苯异丙胺的判别刺激作用。

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摘要

The effect of the 5-HT3 receptor partial agonist MD-354 (meta-chlorophenylguanidine) was examined on the discriminative stimulus produced by (+)amphetamine. Using male Sprague-Dawley rats trained to discriminate 1.0 mg/kg (i.p.) of (+)amphetamine from saline vehicle (VI 15-s schedule of reinforcement) in a two-lever operant procedure for appetitive reward, tests of stimulus generalization (substitution) and antagonism showed that MD-354 neither substituted for, nor antagonized, the amphetamine stimulus at the doses evaluated. Administration of (+)amphetamine doses in combination with a fixed (i.e., 1.0 mg/kg) dose of MD-354 shifted the (+)amphetamine dose-response curve to the left such that, following 0.3 mg/kg of (+)amphetamine, stimulus generalization occurred. Furthermore, MD-354 doses of 0.1, 0.3 and 1.0 mg/kg, but not doses of 0.01, 0.5, 1.5 or 3.0 mg/kg (i.p.), administered in combination with the ED(50) dose (0.33 mg/kg) of (+)amphetamine resulted in stimulus generalization (i.e., >80% drug-appropriate responding). It is concluded that even though MD-354 lacks amphetamine-like central stimulant actions of its own it can modulate the discriminative stimulus effects of (+)amphetamine in rats.
机译:检查了5-HT 3受体部分激动剂MD-354(间氯苯胍)对(+)苯异丙胺产生的区别性刺激的作用。使用训练有素的雄性Sprague-Dawley大鼠在两个杠杆操作程序中从盐水媒介物中区分1.0 mg / kg(ip)的(+)苯异丙胺(VI 15-s强化时间表),以获取奖励,进行刺激普遍性测试(替代) )和拮抗作用表明,在所评估的剂量下,MD-354既不替代苯丙胺刺激也不拮抗苯丙胺刺激。给予(+)苯丙胺剂量与固定(即1.0 mg / kg)的MD-354剂量相结合,使(+)苯丙胺剂量-反应曲线向左移动,以便在0.3 mg / kg的(+)之后苯丙胺,刺激普遍发生。此外,MD-354剂量为0.1、0.3和1.0 mg / kg,但不包括0.01、0.5、1.5或3.0 mg / kg(ip),与ED(50)剂量(0.33 mg / kg)联合使用(+)苯丙胺的使用导致刺激泛化(即> 80%的药物适当响应)。结论是,即使MD-354本身不具有苯丙胺样的中央刺激作用,它也可以调节(+)苯丙胺对大鼠的歧视性刺激作用。

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