Pharmacological specificity of conditioned avoidance response inhibition in rats: inhibition by neuroleptics and correlation to dopamine receptor blockade.
Pharmacological specificity of conditioned avoidance response inhibition in rats: inhibition by neuroleptics and correlation to dopamine receptor blockade.
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DOI：
10.1111/j.1600-0773.1982.tb01032.x
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发表时间：
2009-03
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影响因子：
--
通讯作者：
J. Arnt
中科院分区：
文献类型：
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作者：
J. Arnt
本文研究了36种抗精神病药物对大鼠条件性回避反应（CAR）和非条件性逃避反应（UER）的抑制作用。所有抗精神病药物拮抗CAR的剂量低于那些抑制UER和低于那些诱导僵住症。立体特异性显示在两个案件。发现CAR抑制效力和致僵住效力之间存在显著相关性。此外，苯丙胺诱导的刻板性、体外对3 H-氟哌啶醇结合位点的亲和力和临床效力的抑制与CAR抑制显著相关。顺式氟哌噻吨和氟哌啶醇诱导的CAR和UER抑制可被东莨菪碱减弱，但仅受麦角新碱和哌唑嗪的微弱影响。在测试的多种其他CNS活性化合物中，CAR被α 1-肾上腺素能拮抗剂、苯二氮卓类、巴比妥类、GABA激动剂、吗啡和5-羟色胺激动剂抑制，但在诱导其他运动障碍的剂量下。可以得出结论，CAR抑制是多巴胺受体拮抗剂的敏感试验。然而，在一些精神抑制剂（例如氯氮平、氯普噻吨）中发现的额外α-肾上腺素能活性可能有助于CAR抑制效力。抗精神病药的额外抗毒蕈碱活性可适度减弱CAR抑制，而5-羟色胺受体阻断作用不太重要。
The inhibitory effect of 36 neuroleptic compounds on conditioned avoidance response (CAR) and unconditioned escape response (UER) has been studied in rats. All neuroleptics antagonized CAR in doses below those inhibiting UER and below those inducing catalepsy. Stereospecificity was shown in two cases. Significant correlation was found between CAR inhibitory and cataleptogenic potency. Also inhibition of amphetamine induced stereotypy, affinity to 3H-haloperidol binding sites in vitro and clinical potency was significantly correlated to CAR inhibition. CAR and UER inhibition induced by cis(Z)-flupentixol and haloperidol was attenuated by scopolamine, but was only weakly influenced by methysergide and prazosin. Among a wide range of other CNS active compounds tested, CAR was inhibited by alpha 1-adrenergic antagonists, benzodiazepines, a barbiturate, GABA agonists, morphine and a serotonin agonist, but in doses inducing other motor disturbances. It is concluded that CAR inhibition is a sensitive test for dopamine receptor antagonists. However, additional alpha-adrenergic activity found for some neuroleptics (e.g. clozapine, chlorprothixene) may contribute to the CAR inhibitory potency. Additional antimuscarinic activity of neuroleptics may moderately attenuate CAR inhibition whereas serotonin receptor blockade is of minor importance.