Rech R H, Commissaris R L
Neurosci Biobehav Rev. 1982 Winter;6(4):521-7. doi: 10.1016/0149-7634(82)90035-5.
Indole and phenethylamine-type hallucinogenic drugs were studied in an FR-40 operant behavioral procedure programmed to quantify "pausing,"-a behavioral disruption somewhat specific to hallucinatory drug effects. LSD, DOM, DMT and mescaline showed a potency ratio to produce pausing that is well correlated with the hallucinatory potencies of these agents in man. Furthermore, combinations of the hallucinogens interact with potentiation to cause FR-40 pausing, whereas a variety of non-hallucinogenic psychoactive drugs failed to shift the dose-response patterns of pausing for DOM or LSD. Depletion of brain catecholamines by pretreatment with intraventricular 6-OHDA reduced baseline FR-40 rates and attenuated the disruptive effects of d-amphetamine, but failed to modify the dose-response patterns of indole and phenethylamine hallucinogens. On the other hand, pretreatment with intraventricular 5,7-DHT to deplete brain 5-HT potentiated the pause-producing effects of the hallucinogens, although the disruptive effects of phenobarbital were not altered by this pretreatment. Injection of 5,7-DHT into the medial forebrain bundle at the hypothalamic level slightly potentiated LSD, attenuated DOM, and did not affect the pausing produced by mescaline. Metergoline pretreatment shifted the LSD and DMT dose-response curves for pausing to the right by a factor of 2--3, but shifted the DOM and mescaline dose-response patterns to a much greater extent. Metergoline alone slightly increased FR-40 response rates and decreased pausing from baseline levels. The patterns of imparied FR-40 performance induced by d-amphetamine and phenobarbital were unaltered by pretreatment with metergoline. The indole and phenethylamine classes of hallucinogens appear to disrupt this behavior by an agonistic effect at central 5-HT receptors. However, the two classes of drugs may interact with brain 5-HT systems by somewhat different mechanisms.
在一种FR - 40操作性行为程序中，对吲哚和苯乙胺类致幻药物进行了研究，该程序旨在量化“停顿”——一种对致幻药物效应具有一定特异性的行为干扰。麦角酸二乙酰胺（LSD）、2,5 - 二甲氧基 - 4 - 甲基苯丙胺（DOM）、N,N - 二甲基色胺（DMT）和三甲氧苯乙胺（mescaline）产生停顿的效价与这些药物在人体中的致幻效价高度相关。此外，致幻剂组合相互作用产生增强作用，导致FR - 40停顿，而多种非致幻性精神活性药物未能改变DOM或LSD停顿的剂量 - 反应模式。通过脑室内注射6 - 羟基多巴胺（6 - OHDA）进行预处理来耗尽脑内儿茶酚胺，降低了基线FR - 40速率，并减弱了右旋苯丙胺的干扰作用，但未能改变吲哚和苯乙胺类致幻剂的剂量 - 反应模式。另一方面，脑室内注射5,7 - 二羟色胺（5,7 - DHT）以耗尽脑内5 - 羟色胺（5 - HT），增强了致幻剂产生停顿的作用，尽管这种预处理并未改变苯巴比妥的干扰作用。在下丘脑水平将5,7 - DHT注入内侧前脑束，对LSD有轻微增强作用，但减弱了DOM的作用，并且不影响三甲氧苯乙胺产生的停顿。麦角新碱预处理使LSD和DMT产生停顿的剂量 - 反应曲线向右移动2至3倍，但使DOM和三甲氧苯乙胺的剂量 - 反应模式移动的幅度更大。单独使用麦角新碱会使FR - 40反应速率略有增加，并使停顿较基线水平减少。麦角新碱预处理并未改变右旋苯丙胺和苯巴比妥引起的FR - 40行为表现受损模式。吲哚和苯乙胺类致幻剂似乎通过对中枢5 - HT受体的激动作用来干扰这种行为。然而，这两类药物可能通过略有不同的机制与脑内5 - HT系统相互作用。
