Der Einfluss von S-Ketamin und N,N-dimethyltrytamine (DMT) auf die Präpulsinhibition und die attentive Modulation des Startlereflexes : eine humanexperimentelle Untersuchung zum Modellpsychoseparadigma

Abstract

Prepulse inhibition (PPI) of the acoustic startle reflex is a well established model for sensorimotor gating. Sensorimotor gating and also habituation are considered to serve as mechanisms that protect early stimulus processing and prevent the organism from experiencing sensory overload. Habituation refers to the reduction of the reflex amplitude by presentation of a weak prestimulus 30-500 ms prior to the startle-elicting stimulus. Several studies indicate that PPI does not reflect a pure preattentive mechanism but is also influenced by controlled attentional processes. Pharmacological challenges with hallucinogens are used as model for psychosis in animal and human experimental studies. Remarkably, in contrast to the findings in schizophrenic patients and in animal hallucinogen models of psychosis, previous studies with healthy volunteers demonstrated increased levels of PPI after administration of low to moderate doses of either the antiglutamatergic hallucinogen ketamine or the serotonergic hallucinogen psilocybin. The aim of the present study was to investigate the influence of moderate and high doses of the serotonergic hallucinogen N,N-dimethyltryptamine (DMT) and the NMDA antagonist S-ketamine on PPI and its attentional modulation in humans. Fifteen healthy volunteers were included in a double-blind cross-over study with two doses of DMT and S-ketamine. Effects on PPI and its attentional modulation were investigated. Nine subjects completed both experimental days with two doses of both drugs. S-ketamine increased PPI in both dosages, whereas DMT had no significant effects on PPI. S-ketamine decreased and DMT tended to decrease startle magnitude. There were no significant effects of either drug on the attentional modulation of PPI. In human experimental hallucinogen psychoses, and even with high, clearly psychotogenic doses of DMT or S-ketamine, healthy subjects failed to exhibit the predicted attenuation of PPI. In contrast, PPI was augmented and the startle magnitude was decreased after S-ketamine. These date point to important differences between human hallucinogen models and both animal hallucinogen models of psychosis and naturally occurring schizophrenia