Clozapine's functional mesolimbic selectivity is not duplicated by the addition of anticholinergic action to haloperidol: a brain stimulation study in the rat.
Clozapine's functional mesolimbic selectivity is not duplicated by the addition of anticholinergic action to haloperidol: a brain stimulation study in the rat.
复制标题
氯氮平的功能性中脑边缘选择性不会因氟哌啶醇添加抗胆碱能作用而重复：一项大鼠脑刺激研究。
DOI：
10.1007/bf02246960
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发表时间：
1993
影响因子：
3.4
通讯作者：
Paredes,W
中科院分区：
文献类型：
--
作者：
Gardner,EL;Walker,LS;Paredes,W
本研究探讨了临床上的上级抗精神病药物氯氮平的抗胆碱能效力是否有助于氯氮平的中脑边缘多巴胺（DA）系统的解剖学选择性功能抑制，使用电脑刺激奖励（BSR）的范式，在大鼠，以前已被证明是高度敏感的氯氮平的中脑边缘功能的选择性。大鼠长期给予生理盐水，氯氮平，氟哌啶醇，或氟哌啶醇加抗胆碱能化合物苯海索，和阈值敏感性的中脑边缘和黑质纹状体DA系统进行了评估，使用BSR范式，推断程度的功能DA阻滞产生的慢性药物治疗方案。慢性生理盐水在两个DA系统中均未产生变化。与以前的研究结果一致，慢性氯氮平强烈抑制中脑边缘DA系统，但幸免于黑质纹状体DA系统。也与以前的研究结果一致，慢性氟哌啶醇强烈抑制两个DA系统。与慢性氟哌啶醇单药相比，慢性氟哌啶醇加慢性苯海索在中脑边缘和黑质纹状体DA系统中的抗DA作用减弱。这些结果表明，氯氮平的抗胆碱能效力是不是一个充分的解释其功能性中脑边缘的选择性。
This study examined whether the anticholinergic potency of the clinically superior antipsychotic drug clozapine contributes to clozapine's anatomically-selective functional inhibition of the mesolimbic dopamine (DA) system, using an electrical brain-stimulation reward (BSR) paradigm in rats that has been previously shown to be highly sensitive to clozapine's mesolimbic functional selectivity. Rats were chronically administered saline, clozapine, haloperidol, or haloperidol plus the anticholinergic compound trihexyphenidyl, and threshold sensitivity of the mesolimbic and nigrostriatal DA systems was assessed using the BSR paradigm, to infer degree of functional DA blockade produced by the chronic drug regimens. Chronic saline produced no change in either DA system. Congruent with previous findings, chronic clozapine powerfully inhibited the mesolimbic DA system but spared the nigrostriatal DA system. Also congruent with previous findings, chronic haloperidol powerfully inhibited both DA systems. Compared to chronic haloperidol alone, chronic haloperidol plus chronic trihexyphenidyl exerted diminished anti-DA action in both the mesolimbic and nigrostriatal DA systems. These results suggest that clozapine's anticholinergic potency is not an adequate explanation for its functional mesolimbic selectivity.