Behavioral effects of ketamine, an NMDA glutamatergic antagonist, in non-human primates.

Y Shiigi; D E Casey

doi:10.1007/s002130051089

Behavioral effects of ketamine, an NMDA glutamatergic antagonist, in non-human primates.

Y Shiigi, D E Casey

Psychopharmacology September 1, 1999 DOI: 10.1007/s002130051089 (opens in new tab)

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Characteristics	Experimental animal study Peer reviewed
Sample size	32
Population	Cebus monkeys previously sensitized to neuroleptics
Intervention	Ketamine
Dose	a wide range of doses spanning the clinical effect range from threshold effects to full anesthesia
Topics	Esketamine Ketamine
Key findings	Ketamine produced dose-related increases in parkinsonian bradykinesia and dystonia, as well as salivation, and decreases in locomotor activity and reactivity.

Abstract

The dopamine hypothesis is the most widely investigated theory underlying schizophrenia and the mechanisms of action for antipsychotic drugs. However, recent studies call into question this proposal. Thus, the focus has turned towards other mechanisms, one of which has been glutamatergic systems. Phencyclidine (PCP), a potent NMDA receptor antagonist, causes a schizophrenic-like psychosis in normal volunteers and exacerbates psychotic symptoms in patients with schizophrenia. Ketamine, like PCP, is a non-competitive NMDA receptor antagonist, which is short acting and has been used as a dissociative anesthetic as well as a research tool in psychosis. To clarify the role of NMDA antagonists further and to develop an animal model of these actions, ketamine was studied across a range of behaviors in Cebus monkeys. Thirty-two (six male, 26 female) Cebus monkeys, which were previously sensitized to neuroleptics, were tested with a wide range of doses of ketamine that spanned the clinical effect range from threshold effects to full anesthesia. Behaviors scored included sedation/arousal, locomotor activity, extrapyramidal symptoms of parkinsonism and dystonia, as well as reactivity. Ketamine produced dose-related increases in parkinsonian bradykinesia and dystonia as well as salivation. There were dose-related decreases in locomotor activity and reactivity to environmental stimuli. These effects had short time courses and steep dose-response curves. These results suggest that ketamine-induced behavioral effects in non-human primates offer a model for studying a glutamatergic role in motor and mental function such as attention or perception.

Comparable studies

Other preclinical and animal studies on ketamine, most cited first.

Study	Year	Design
mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats	2010	Observational study
Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats	1997	Dose-response study with microdialysis and behavioral testing
NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice	2016	Preclinical study
The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats	1983	Experimental study
R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice	2015	Experimental study

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