Trulson M E, Jacobs B L
J Pharmacol Exp Ther. 1979 Nov;211(2):375-84.
Chronic administration of amphetamine to cats (twice daily, in doses increasing from 5 to 15 mg/kg over a 10-day period) elicited a number of behaviors, e.g., limb flick and abortive groom, characteristic of the action of hallucinogenic drugs and dependent on a depression of central serotonergic neurotransmission. This drug treatment produced large decreases (-40 to -60%) in central nervous system serotonin (5-HT) and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), when measured either 6 or 24 hr after the last amphetamine injection. The rate of limb flicking returned to a predrug level approximately 5 days after drug withdrawal, at which time 5-HT and 5-HIAA levels had returned to within 30 to 40% of base line. Both 5-HT and 5-HIAA returned to base-line levels within 14 days after drug withdrawal. Norepinephrine (NE), dopamine (DA) and DA metabolites were decreased 60 to 95% by chronic amphetamine treatment and showed little recovery within the 14 days after drug withdrawal. A second experiment examined the latency to onset of the behavioral and neurochemical changes with a constant dose of amphetamine (7.5 mg/kg, twice daily). Limb flicking was significantly increased above base-line levels following 3 days of amphetamine administration, at which time 5-HT and 5-HIAA levels were decreased 30 to 40%. NE, DA and DA metabolites were decreased approximately 50 to 90% by this treatment regimen. A third experiment examined the effects of a low dose of amphetamine (3.75 mg/kg), injected more frequently (every 6 hr for 6 days), to approximate the administration pattern in human amphetamine abuse. This treatment produced significant increases in limb flicking and abortive grooming on days 5 and 6 and resulted in 30 to 40% depletions of 5-HT and 5-HIAA. NE, DA and DA metabolites were decreased by approximately 50 to 90%. These data are discussed in relation to a role for serotonin in amphetamine psychosis and schizophrenia.
对猫长期给予苯丙胺（每天两次，剂量在10天内从5毫克/千克增加到15毫克/千克）引发了一些行为，例如肢体轻弹和不完全梳理毛发，这些行为是致幻药物作用的特征，并且依赖于中枢5-羟色胺能神经传递的抑制。在最后一次注射苯丙胺后6小时或24小时测量时，这种药物治疗使中枢神经系统5-羟色胺（5-HT）及其主要代谢产物5-羟吲哚乙酸（5-HIAA）大幅下降（-40%至-60%）。停药后约5天，肢体轻弹的频率恢复到用药前水平，此时5-HT和5-HIAA水平已恢复到基线水平的30%至40%以内。停药后14天内，5-HT和5-HIAA均恢复到基线水平。长期给予苯丙胺治疗使去甲肾上腺素（NE）、多巴胺（DA）及其代谢产物减少60%至95%，停药后14天内几乎没有恢复。第二个实验用恒定剂量的苯丙胺（7.5毫克/千克，每天两次）研究行为和神经化学变化开始出现的潜伏期。给予苯丙胺3天后，肢体轻弹明显高于基线水平，此时5-HT和5-HIAA水平下降了30%至40%。通过这种治疗方案，NE、DA及其代谢产物减少了约50%至90%。第三个实验研究了低剂量苯丙胺（3.75毫克/千克）更频繁注射（每6小时注射一次，共6天）的效果，以模拟人类滥用苯丙胺的给药模式。这种治疗在第5天和第6天使肢体轻弹和不完全梳理毛发显著增加，并导致5-HT和5-HIAA耗竭30%至40%。NE、DA及其代谢产物减少了约50%至90%。将根据5-羟色胺在苯丙胺精神病和精神分裂症中的作用来讨论这些数据。
