Comparative and interactive human psychopharmacologic effects of ketamine and amphetamine - Implications for glutamatergic and dopaminergic model psychoses and cognitive function
Comparative and interactive human psychopharmacologic effects of ketamine and amphetamine - Implications for glutamatergic and dopaminergic model psychoses and cognitive function
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DOI：
10.1001/archpsyc.62.9.985
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发表时间：
2005-09-01
影响因子：
--
通讯作者：
D'Souza, DC
中科院分区：
文献类型：
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作者：
Krystal, JH;Perry, EB;D'Souza, DC
背景资料：在健康个体中，盐酸氯胺酮和硫酸苯丙胺产生类似内源性精神病的认知、行为和主观效应。研究这些药物的比较和相互作用可能会提供谷氨酸和单胺系统在精神病和认知中的作用的见解。目的：直接比较氯胺酮和安非他明的作用，并探讨其在个体内的相互作用。设计：安慰剂对照，随机，双盲精神药理学试验。设置和参与者：从社区招募了41名健康个体，他们完成了长达4天的测试。在每个测试日，参与者接受安非他明（硫酸苯丙胺，0.25 mg/kg或生理盐水，1分钟输注）和氯胺酮（氯胺酮0.23 mg/kg的1分钟静脉输注，随后0.5 mg/kg的1小时输注或相同的盐水推注和输注）。安非他明和氯胺酮输液的顺序是随机的。结果：在研究的剂量，氯胺酮和安非他明产生阳性症状和欣快感。然而，只有氯胺酮才能引起知觉变化，只有安非他明才能刺激敌意、夸大和躯体关注。安非他明和氯胺酮产生概念混乱，但只有氯胺酮产生具体的想法和不寻常的举止。氯胺酮产生阴性症状并破坏延迟回忆。氯胺酮和安非他明表现出3种类型的交互作用：（1）安非他明衰减氯胺酮产生的工作记忆的损害;（2）安非他明和氯胺酮有相加作用的思维障碍，觉醒，和欣快症;和（3）安非他明和氯胺酮有小于相加的影响psycho.Conclusions：这些研究结果牵连N-甲基-D-天冬氨酸谷氨酸受体和多巴胺系统在精神病。然而，谷氨酸和多巴胺可能对精神病，思维障碍和欣快症有不同的贡献。关于认知功能障碍的药物开发，氯胺酮和安非他明的相互作用模式与以下假设一致：促进前额叶皮质多巴胺水平将减轻与N-甲基-D-天冬氨酸受体功能缺陷相关的一些认知障碍。
Background: In healthy individuals, ketamine hydrochloride and amphetamine sulfate produce cognitive, behavioral, and subjective effects resembling endogenous psychoses. Studying the comparative and interactive effects of these agents may provide insights into the roles of the glutamate and monoamine systems in psychosis and cognition.Objectives: To directly compare the effects of ketamine and amphetamine and to explore their interactive effects within individuals.Design: Placebo-controlled, randomized, double-blind psychopharmacologic trial.Setting and Participants: Forty-one healthy individuals recruited from the community who completed up to 4 test days.Main Outcome Measures: On each test day, participants received amphetamine (a I-minute infusion of amphetamine sulfate, 0.25 mg/kg, or saline) and ketamine (a I-minute intravenous infusion of ketamine, 0.23 mg/kg, followed by a I-hour infusion of 0.5 mg/kg or an identical saline bolus and infusion). The order of amphetamine and ketamine infusions was randomized.Results: At the doses studied, ketamine and amphetamine produced positive symptoms and euphoria. However, perceptual changes were produced only by ketamine, and hostility, grandiosity, and somatic concern were stimulated only by amphetamine. Amphetamine and ketamine produced conceptual disorganization, but only ketamine produced concrete ideation and unusual mannerisms. Ketamine produced negative symptoms and disrupted delayed recall. Ketamine and amphetamine showed 3 types of interactive effects: (1) amphetamine attenuated the impairment of working memory produced by ketamine; (2) amphetamine and ketamine had additive effects on thought disorder, arousal, and euphoria; and (3) amphetamine and ketamine had less-than-additive effects on psychosis.Conclusions: These findings implicate N-methyl-D-aspartate glutamate receptors and dopamine systems in psychosis. However, glutamate and dopamine may differentially contribute to psychosis, thought disorder, and euphoria. Regarding medication development for cognitive dysfunction, the pattern of the interactive effects of ketamine and amphetamine is consistent with the hypothesis that facilitation of prefrontal cortical dopamine levels would attenuate some cognitive impairments associated with deficits in N-methyl-D-aspartate receptor function.