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.
Imre
Gabor
G
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
Fokkema
Dirk S
DS
Den Boer
Johan A
JA
Ter Horst
Gert J
GJ
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