Stefanovic Ana, Brandner Brigitta, Klaassen Elissa, Cregg Roman, Nagaratnam Mayavaty, Bromley Lesley M, Das Ravi K, Rossell Susan L, Morgan Celia J A, Curran H Valerie
Clinical Psychopharmacology Unit, University College London, London, United Kingdom.
J Clin Psychopharmacol. 2009 Apr;29(2):124-33. doi: 10.1097/JCP.0b013e31819a4b91.
Acute administration of the N-methyl-D-aspartate receptor antagonist ketamine induces schizophrenia-like symptoms in healthy volunteers; furthermore, a window on ketamine's chronic effects is provided by regular recreational users. The current study utilized both acute ketamine administration in healthy volunteers and chronic ketamine abusers to investigate semantic processing, one of the key cognitive deficits in schizophrenia. Semantic processing was examined using a semantic priming paradigm. In experiment 1, acute effects of low (75 ng/mL) and high (150 ng/mL) ketamine doses were compared in a placebo-controlled double-blind independent group design with 48 participants. In experiment 2, 19 regular recreational ketamine users were compared with 19 ketamine-naive polydrug controls and 26 non-drug-using controls. In both experiments, semantic priming parameters were manipulated to distinguish between ketamine's effects on (1) automatic and strategic processing and (2) the facilitation and inhibition components of semantic priming for strongly (directly) related primes and targets. Acute effects of ketamine on semantic priming for weakly (indirectly) related primes and targets were also assessed in experiment 1. Acutely, ketamine impaired the employment of strategic mechanisms but not automatic processing within both the direct and indirect semantic priming tasks. Acute ketamine administration also induced clear schizophrenia-like symptoms. Schizotypy traits in the cognitive and perceptual domains tended to correlate with increased semantic priming in long-term ketamine users. In summary, acute and chronic ketamine-induced changes partially mirrored the findings on semantic priming in schizophrenia.
给健康志愿者急性注射 N-甲基-D-天冬氨酸受体拮抗剂氯胺酮会诱发类似精神分裂症的症状；此外，经常吸食氯胺酮的人能让我们了解其长期影响。本研究通过对健康志愿者急性注射氯胺酮以及研究长期滥用氯胺酮的人，来探究语义加工，这是精神分裂症关键的认知缺陷之一。使用语义启动范式来检验语义加工。在实验 1 中，采用安慰剂对照双盲独立组设计，将 48 名参与者分为低剂量（75 纳克/毫升）和高剂量（150 纳克/毫升）氯胺酮组，比较急性效应。在实验 2 中，将 19 名经常吸食氯胺酮的人、19 名未接触过氯胺酮的多药滥用对照者和 26 名不使用药物的对照者进行比较。在两个实验中，均操纵语义启动参数，以区分氯胺酮对（1）自动加工和策略性加工，以及（2）强（直接）相关启动刺激和目标刺激的语义启动促进和抑制成分的影响。实验 1 还评估了氯胺酮对弱（间接）相关启动刺激和目标刺激语义启动的急性效应。急性情况下，氯胺酮在直接和间接语义启动任务中损害了策略机制的运用，但未影响自动加工。急性注射氯胺酮还诱发了明显的类似精神分裂症的症状。长期使用氯胺酮者在认知和感知领域的分裂型人格特质往往与语义启动增加相关。总之，急性和慢性氯胺酮诱发的变化部分反映了精神分裂症语义启动方面的研究结果。
