Loss of contact with the external world is due to the blockade of NMDA receptors involved in sensory transmission. NMDA receptors play a central role in the transmission of incoming signals from all sensory modalities. NMDA receptors form the molecular substrate of a gate and have their highest concentration in the hippocampus, a part of the medial temporal lobe where data from the external world is integrated with internal programs. NMDA antagonists close this gated channel to incoming data.
From a theoretical, neurophysiological point of view, NMDA antagonists do not suppress the perception and processing of sensory stimuli. Sensory stimuli without any nociceptive character are transmitted up to primary sensory cortices under anaesthesia. There is, however, a dissociation between the primary sensory cortices and the secondary evaluation of sensory stimuli. This allows for the clinical observation of dreams and hallucinations during general anaesthesia.
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