ANALYZING MECHANISM(S) OF HALLUCINOGENIC DRUG-ACTION WITH DRUG DISCRIMINATION PROCEDURES
ANALYZING MECHANISM(S) OF HALLUCINOGENIC DRUG-ACTION WITH DRUG DISCRIMINATION PROCEDURES
复制标题
DOI：
10.1016/0149-7634(82)90036-7
复制
发表时间：
1982-01-01
影响因子：
8.2
通讯作者：
HOLOHEAN, AM
中科院分区：
文献类型：
--
作者：
APPEL, JB;WHITE, FJ;HOLOHEAN, AM
通过回顾LSD的研究，说明了使用药物辨别（DD）程序来分析致幻药物和相关药物的作用机制的一些优点。因为它们确保药物诱导的内感受状态的改变成为具有生物学意义的线索，所以这些程序是可靠的，稳健的，灵敏的和特异性的。关于LSD，许多DD实验表明：虽然致幻剂替代（模拟）LSD（在大鼠中），但这种替代并不能预测致幻效力（在人类中），但确实预测了作用机制的相似性; LSD的行为（体内）效应与其某些同类物不同，主要由中枢介导，多巴胺能（5-HT）神经元机制，尽管LSD也可能具有（次级）多巴胺（DA）激动剂特性;这些LSD-5-HT相互作用的位点和性质都不清楚：可能涉及来自中缝背侧的B-7、B-8和B-9区域的细胞;用消耗5-HT并增加体外3 H-LSD立体特异性结合的试剂（对氯苯丙氨酸; 5，7-二羟色胺）预处理增强体内对LSD的敏感性。
Some of the advantages of using drug discrimination (DD) procedures to analyze the mechanisms of action of hallucinogenic and related drugs were illustrated by reviewing research with LSD. Because they ensure that drug-induced alterations in interoceptive state become biologically meaningful cues, these procedures are reliable, robust, sensitive and specific. With reference to LSD, many DD experiments suggest: that while hallucinogens substitute for (mimic) LSD (in rats), such substitution does not predict hallucinogenic potency (in humans) but does predict similarities in mechanism(s) of action; the behavioral (in vivo) effects of LSD, unlike those of some of its congeners, are mediated primarily by central, serotonergic (5-HT) neuronal mechanism although LSD may also have (secondary) dopamine(DA) agonist properties; both the locus and the nature of these LSD-5-HT interactions are unclear: cells arising from B-7, B-8 and B-9 regions of the dorsal-medial raphe may be involved; pretreatment with agents that deplete 5-HT and increase the stereospecific binding of 3H-LSD in vitro (p-chlorophenylalanine; 5,7-dihydroxytryptamine) enhance sensitivity to LSD in vivo.