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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Mixed D2/5-HT2 antagonism differentially affects apomorphine- and amphetamine-induced stereotyped behavior.
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Mixed D2/5-HT2 antagonism differentially affects apomorphine- and amphetamine-induced stereotyped behavior.

机译：混合的D2 / 5-HT2拮抗作用差异性地影响阿扑吗啡和苯丙胺诱导的刻板行为。

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摘要

Evidence supports the hypothesis that psychostimulant stereotypy is mediated through postsynaptic dopamine receptors. Given the recent findings of behavioral, neurochemical and electrophysiological studies showing 5-HT2 modulation of dopamine systems, a series of experiments were undertaken to assess the ability of D2 and 5-HT2 antagonists to reverse apomorphine and amphetamine stereotypy in the rat. Haloperidol reduced stereotyped behavior induced by d-amphetamine (50% reduction with 0.162 mg/kg) and apomorphine (50% reduction with 0.112 mg/kg) MDL 28,133A, a mixed D2/5-HT2 antagonist, also reduced stereotypy in the apomorphine group (50% reduction with 3.89 mg/kg) but was much less effective in antagonizing the effects of d-amphetamine (not even a 25% reduction with 9.0 mg/kg). MDL 100,907, a selective 5-HT2 antagonist, was ineffective at reducing stereotyped behavior induced by either stimulant. Thus, 5-HT2 modulation of dopaminergic activity was not demonstrated in the case of psychostimulant stereotypy. Furthermore, 5-HT2 antagonism did not induce stereotypy, as has been proposed in some models. These findings provide further support for the hypothesis that antipsychotic medications with high affinity for 5-HT2 receptors do not interfere with the regulation of the nigrostriatal dopaminergic system and, therefore, would be less likely to produce extrapyramidal side effects.
机译：证据支持以下假设：精神刺激性刻板印象是通过突触后多巴胺受体介导的。鉴于最近的行为，神经化学和电生理研究发现显示多巴胺系统具有5-HT2调节作用，因此进行了一系列实验来评估D2和5-HT2拮抗剂逆转大鼠阿扑吗啡和苯丙胺定型能力。氟哌啶醇减少了由d-苯异丙胺（减少0.162 mg / kg减少50％）和阿扑吗啡（减少0.112 mg / kg减少50％）引起的刻板印象行为MDL 28,133A，一种混合​​的D2 / 5-HT2拮抗剂，也减少了阿扑吗啡的刻板印象组（3.89 mg / kg降低50％），但拮抗d-苯异丙胺的效果差得多（甚至9.0 mg / kg降低25％）。 MDL 100,907（一种选择性的5-HT2拮抗剂）在减少任何一种刺激物诱导的刻板行为方面均无效。因此，在精神刺激性刻板印象的情况下，没有证明5-HT 2对多巴胺能活性的调节。而且，5-HT2拮抗作用没有引起刻板印象，正如某些模型所提出的那样。这些发现为以下假设提供了进一步的支持：对5-HT2受体具有高亲和力的抗精神病药物不会干扰黑质纹状体多巴胺能系统的调节，因此，产生锥体束外副作用的可能性较小。

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