Dose-response characteristics of ketamine effect on locomotion, cognitive function and central neuronal activity.
The present dose-response study sought to determine the effects of subanesthetic dosages (4-16 mg/kg) of ketamine on locomotion, sensorimotor gating (PPI), working memory, as well as c-fos expression in various limbic regions implicated in the pathogenesis of schizophrenia. In addition, we examined whether ketamine-induced locomotion was influenced by the dark/light cycle. We found that ketamine increased locomotor activity in a dose dependent manner, but found no influence of the dark-light cycle. Additionally, ketamine dose-dependently interrupted PPI, resulting in prepulse facilitation at doses of 8 and 12 mg/kg. The dose of 12 mg/kg also induced impairments in working memory assessed by the discrete-trial delayed-alternation task. C-fos expression indicated that the dose-dependent behavioral effects of ketamine might be related to changes in the activity of limbic regions, notably hippocampus and amygdala.
Department of Psychiatry, P7.16, Medical Center, University of Groningen, Hanzeplein 1, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. g.imre@med.umcg.nl
Gabor
G
Imre
Dirk S
DS
Fokkema
Johan A
JA
Den Boer
Gert J
GJ
Ter Horst
D000161:Acoustic Stimulation / Q000379:methods; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000166:cytology*; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D007649:Ketamine / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000187:drug effects / Q000528:radiation effects; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D016760:Proto-Oncogene Proteins c-fos; D007649:Ketamine