Fiorella D, Helsley S, Lorrain D S, Rabin R A, Winter J C
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University, New York, USA.
Psychopharmacology (Berl). 1995 Oct;121(3):364-72. doi: 10.1007/BF02246076.
The present study was designed to determine the effects of p-chlorophenylalanine (PCPA) and p-chloroamphetamine (PCA) administration on (1) the levels of serotonin (5-hydroxytryptamine, 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in rat brain, (2) the sensitivity of LSD-trained rats to the stimulus effects of LSD, and (3) the maximal levels of 5-HT2A and 5-HT2C receptor mediated phosphoinositide (PI) hydrolysis in rat brain. PCA and PCPA both produced a significant depletion of whole brain 5-HT and 5-HIAA concentrations. The depletion of serotonin with PCPA, but not PCA, resulted in supersensitivity of LSD-trained subjects to the stimulus effects of LSD. Neither PCPA nor PCA treatment altered the maximal level of 5-HT2A receptor-mediated PI hydrolysis. However, PCPA, but not PCA, treatment resulted in a significant upregulation (46%, P < 0.05) of the maximal level of 5-HT2C receptor mediated PI hydrolysis. These data suggest that upregulation of the 5-HT2C receptor mediates the supersensitivity to LSD discriminative stimulus which follows the depletion of central nervous system serotonin by PCPA.
本研究旨在确定给予对氯苯丙氨酸（PCPA）和对氯苯丙胺（PCA）对以下方面的影响：（1）大鼠脑中血清素（5-羟色胺，5-HT）和5-羟吲哚乙酸（5-HIAA）的水平；（2）接受过LSD训练的大鼠对LSD刺激作用的敏感性；（3）大鼠脑中5-HT2A和5-HT2C受体介导的磷酸肌醇（PI）水解的最大水平。PCA和PCPA均导致全脑5-HT和5-HIAA浓度显著降低。PCPA而非PCA导致的血清素耗竭，使接受过LSD训练的受试者对LSD的刺激作用产生超敏反应。PCPA和PCA处理均未改变5-HT2A受体介导的PI水解的最大水平。然而，PCPA而非PCA处理导致5-HT2C受体介导的PI水解的最大水平显著上调（46%，P<0.05）。这些数据表明，5-HT2C受体的上调介导了对LSD辨别刺激的超敏反应，这种超敏反应发生在PCPA导致中枢神经系统血清素耗竭之后。
