Neuropsychopharmacology and Brain Imaging, Clinic of Affective Disorders and General Psychiatry, University Hospital of Psychiatry, University of Zurich, Zurich 8008, Switzerland.
J Neurosci. 2013 Jun 19;33(25):10544-51. doi: 10.1523/JNEUROSCI.3007-12.2013.
Visual illusions and hallucinations are hallmarks of serotonergic hallucinogen-induced altered states of consciousness. Although the serotonergic hallucinogen psilocybin activates multiple serotonin (5-HT) receptors, recent evidence suggests that activation of 5-HT2A receptors may lead to the formation of visual hallucinations by increasing cortical excitability and altering visual-evoked cortical responses. To address this hypothesis, we assessed the effects of psilocybin (215 μg/kg vs placebo) on both α oscillations that regulate cortical excitability and early visual-evoked P1 and N170 potentials in healthy human subjects. To further disentangle the specific contributions of 5-HT2A receptors, subjects were additionally pretreated with the preferential 5-HT2A receptor antagonist ketanserin (50 mg vs placebo). We found that psilocybin strongly decreased prestimulus parieto-occipital α power values, thus precluding a subsequent stimulus-induced α power decrease. Furthermore, psilocybin strongly decreased N170 potentials associated with the appearance of visual perceptual alterations, including visual hallucinations. All of these effects were blocked by pretreatment with the 5-HT2A antagonist ketanserin, indicating that activation of 5-HT2A receptors by psilocybin profoundly modulates the neurophysiological and phenomenological indices of visual processing. Specifically, activation of 5-HT2A receptors may induce a processing mode in which stimulus-driven cortical excitation is overwhelmed by spontaneous neuronal excitation through the modulation of α oscillations. Furthermore, the observed reduction of N170 visual-evoked potentials may be a key mechanism underlying 5-HT2A receptor-mediated visual hallucinations. This change in N170 potentials may be important not only for psilocybin-induced states but also for understanding acute hallucinatory states seen in psychiatric disorders, such as schizophrenia and Parkinson's disease.
视觉幻觉和错觉是血清素能致幻剂引起的意识改变状态的标志。尽管血清素能致幻剂裸盖菇素激活多种血清素（5-HT）受体，但最近的证据表明，通过增加皮质兴奋性和改变视觉诱发的皮质反应，激活 5-HT2A 受体可能导致视觉幻觉的形成。为了验证这一假设，我们评估了裸盖菇素（215μg/kg 与安慰剂）对健康人体α 振荡（调节皮质兴奋性）和早期视觉诱发 P1 和 N170 电位的影响。为了进一步区分 5-HT2A 受体的特定贡献，受试者还接受了选择性 5-HT2A 受体拮抗剂酮色林（50mg 与安慰剂）的预处理。我们发现，裸盖菇素强烈降低了顶枕部α 功率值，从而阻止了随后的刺激引起的α 功率下降。此外，裸盖菇素强烈降低了与视觉知觉改变（包括视觉幻觉）相关的 N170 电位。所有这些效应均被 5-HT2A 拮抗剂酮色林的预处理阻断，表明裸盖菇素激活 5-HT2A 受体强烈调节视觉处理的神经生理和现象学指标。具体来说，通过调节α 振荡，5-HT2A 受体的激活可能会诱导一种处理模式，其中刺激驱动的皮质兴奋被自发神经元兴奋所淹没。此外，观察到的 N170 视觉诱发电位的降低可能是 5-HT2A 受体介导的视觉幻觉的关键机制。N170 电位的这种变化不仅对裸盖菇素诱导的状态很重要，而且对理解精神障碍（如精神分裂症和帕金森病）中出现的急性幻觉状态也很重要。
