The effects of low dose ketamine on sensory gating, neuroendocrine secretion and behavior in healthy human subjects

• Published in: Psychopharmacologia Vol. 137; no. 3; pp. 271 - 281
• Main Authors: VAN BERCKEL, B. N. M, ORANJE, B, VAN REE, J. M, VERBATEN, M. N, KAHN, R. S
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.06.1998; Springer Nature B.V
• Subjects: Adult; Analgesia; Arousal - drug effects; Attention - drug effects; Biological and medical sciences; Blood pressure; Channel gating; Cortisol; Cross-Over Studies; Double-Blind Method; Drug therapy; Drug toxicity and drugs side effects treatment; Electroencephalography - drug effects; Enantiomers; Event-related potentials; Evoked Potentials, Auditory - drug effects; Excitatory Amino Acid Antagonists - pharmacology; Glutamate receptors; Glutamatergic transmission; Glutamic acid receptors (ionotropic); Heart rate; Homovanillic acid; Homovanillic Acid - blood; Hormones; Humans; Hydrocortisone - blood; Ketamine; Ketamine - pharmacology; Luteinizing hormone; Luteinizing Hormone - drug effects; Male; Medical sciences; Mental disorders; Miscellaneous (drug allergy, mutagens, teratogens...); N-Methyl-D-aspartic acid receptors; Neuroendocrine system; Pharmacology. Drug treatments; Plasma levels; Psychiatric Status Rating Scales; Receptors, N-Methyl-D-Aspartate - drug effects; Reflex, Startle - drug effects; Schizophrenia; Secretion; Sensorimotor gating; Withdrawal; Human; Intravenous administration; Pathophysiology; Toxicity; Electrophysiology; Schizophrenia; Startle reflex; Normal; Psychosis; Selective attention; Ketamine; Attentional disorder; Auditory evoked potential; Information processing; Antagonist; NMDA receptor; Gating
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s002130050620

Recently, much interest has been given to the role of glutamatergic N-methyl-D-aspartate receptors (NMDA) in sensory gating, such as prepulse inhibition (PPI) and reduction of the P50 evoked response potential (ERP). Currently, mainly animal data are available describing the role of NMDA receptors in these stimulus evaluation processes. Human data are virtually lacking and are potentially important, for instance for the understanding of sensory gating deficits observed in schizophrenia. Therefore, the effects of the NMDA antagonist ketamine, in a dose of 0.3 mg/kg i.v., on concurrent assessment of PPI and P50 reduction was studied in 18 healthy male volunteers. Ketamine was administered in a pseudo-steady state model with a subacute loading dose. In addition, the effects of ketamine on behavior, vital signs, homovanillic acid (HVA) plasma levels and secretion of cortisol and luteinizing hormone (LH) were also determined. Ketamine did not significantly alter PPI or the reduction of the P50 ERP. A small but significant increase in Brief Psychiatric Rating Scale (BPRS) total scores and BPRS composite scores "thinking disorder" and "withdrawal/retardation" was observed. Several subjects experienced visual perceptional alterations, but complex hallucinations did not occur. Ketamine induced mild analgesia and coordination problems. In addition, ketamine induced a marked rise in cortisol secretion, while LH secretion was not affected. Finally, systolic and diastolic, blood pressure and heart rate increased during ketamine infusion. Although in humans NMDA receptors may not be involved in the regulation of PPI and P50 reduction, the most likely explanation for the lack of effect of ketamine on these sensory gating paradigms is the dose used in this experiment. However, using a higher dose is hampered by the aspecificity of racemic ketamine. Future studies should use the enantiomer S-ketamine, which is more specific to NMDA receptors, to evaluate the involvement of NMDA receptors in these neurophysiological processes further.