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...

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Bibliographic Details
Published in:Brain research bulletin 2006-04, Vol.69 (3), p.338-345
Main Authors: Imre, Gabor, Fokkema, Dirk S., Boer, Johan A. Den, Ter Horst, Gert J.
Format: Article
Language:English
Subjects:
Acoustic Stimulation - methods
Animals
Behavior, Animal - drug effects
Brain - cytology
c-fos
Cognition - drug effects
Cognition - physiology
Dose-Response Relationship, Drug
Excitatory Amino Acid Antagonists - pharmacology
Gene Expression Regulation - drug effects
Hyperlocomotion
Immunohistochemistry - methods
Ketamine
Ketamine - pharmacology
Light/dark cycle
Limbic system
Locomotion - drug effects
Locomotion - physiology
Male
Memory, Short-Term - drug effects
Neural Inhibition - drug effects
Neurons - drug effects
PPI
Proto-Oncogene Proteins c-fos - metabolism
Rats
Rats, Wistar
Reflex, Startle - drug effects
Reflex, Startle - radiation effects
Schizophrenia
Time Factors
Working memory
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Summary: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.
ISSN:0361-9230
1873-2747
DOI:10.1016/j.brainresbull.2006.01.010