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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Effects of antimuscarinic antiparkinsonian drugs on brightness discrimination performance in rats.
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Effects of antimuscarinic antiparkinsonian drugs on brightness discrimination performance in rats.

机译：抗毒蕈碱类抗帕金森病药物对大鼠亮度分辨能力的影响。

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Biperiden (BPR) and trihexyphenidyl (THP), the current antimuscarinic drugs of choice in the management of parkinsonism, have been shown to exert anticonvulsant effects induced by poisoning by the organophosphorus compound soman. The present study was undertaken to evaluate the effects of these drugs on performance of a simple light-intensity discrimination task in rats under a tandem schedule of fixed-ratio (FR) reward/ differential-reinforcement-of-low-rate (DRL) nonreward contingencies, for water reinforcement in 2-h experimental sessions. Both BPR (0.125-2.0 mg/kg, SC) and THP (0.25-8.0 mg/kg, SC) in general decreased overall reinforcement rates in a similar dose dependent and parallel manner, concurrent with increased overall nonreinforced responses in an inverted U-shaped dose-response relationship. Lower doses of BPR (0.125-0.5 mg/kg) and and THP (0.25-2.0 mg/kg) produced a moderate reduction in reinforcement (> or = 50% of baseline controls), which was correlated well with increases in nonreinforced responses emitted, whereas, higher doses of BPR (> 0.5 mg/kg) and TPH (> or = 2.0 mg/kg) markedly decreased reinforcements, which mainly resulted from the pausing of responding in the presence of stereotyped behavior. The behavioral disruption induced by BPR was much more rapid than that induced by THP. The ED50 values (0.6 mg/kg vs. 1.3 mg/kg, respectively) and parallel dose-effect curves suggest that these drugs have similar efficacy, and that BPR is about twice as potent as THP, a ranking that corresponds with their binding affinity at M-1 muscarinic acetylcholine receptors in rat cerebral cortex. Based on the similarity between the anticonvulsant doses of these drugs and the maximal doses that in this study did not disrupt operant responses (0.125 mg/kg vs. 0.25 mg/kg, respectively), it is suggested that both drugs may be useful in protection against seizures produced by the cholinesterase inhibitor soman. Overall, these results suggest that this multiple schedule operant contingency may have promise as a behavioral model to identify the therapeutic or toxic potentials of centrally acting antimuscarinic antiparkinsonian drugs based on their congnitive side effects.
机译：Biperiden（BPR）和Trihexyphenidyl（THP）是目前在帕金森氏病治疗中选择的抗毒蕈碱药物，已显示出有机磷化合物梭曼中毒引起的惊厥作用。本研究旨在评估这些药物对固定比率（FR）奖励/低速差分强化（DRL）非奖励串联计划中大鼠简单光强度辨别任务的执行效果紧急情况，在2小时的实验中用于补水。一般而言，BPR（0.125-2.0 mg / kg，SC）和THP（0.25-8.0 mg / kg，SC）均以相似的剂量依赖性和平行方式降低总体增强率，同时在倒U型中总体非增强反应增加形状的剂量反应关系。较低剂量的BPR（0.125-0.5 mg / kg）和THP（0.25-2.0 mg / kg）产生了中等程度的增强减少（>或=基线对照的50％），这与释放的非增强反应密切相关，而较高剂量的BPR（> 0.5 mg / kg）和TPH（>或= 2.0 mg / kg）显着降低了增强作用，这主要是由于在存在刻板行为的情况下暂停了响应。 BPR引起的行为中断比THP引起的行为中断快得多。 ED50值（分别为0.6 mg / kg和1.3 mg / kg）和平行的剂量效应曲线表明，这些药物具有相似的功效，并且BPR的效力约为THP的两倍，这一等级与其结合亲和力相对应在大鼠大脑皮层的M-1毒蕈碱型乙酰胆碱受体根据这些药物的抗惊厥剂量与本研究中不会干扰手术反应的最大剂量（分别为0.125 mg / kg和0.25 mg / kg）之间的相似性，建议这两种药物都可能对保护患者有用对抗胆碱酯酶抑制剂梭曼产生的癫痫发作。总体而言，这些结果表明，这种多计划的操作偶然性可能有望作为一种行为模型，根据其认知上的副作用确定中枢性抗毒蕈碱型抗帕金森病药物的治疗或毒性潜力。

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