Skip to content

Ketamine Induces Dopamine-Dependent Depression of Evoked Hippocampal Activity in the Nucleus Accumbens in Freely Moving Rats

Mark J. Hunt, Karima Kessal, Rene Garcia

Journal of Neuroscience January 12, 2005 DOI: 10.1523/jneurosci.3800-04.2005 (opens in new tab)

Relevant Not relevant

Study at a glance

AI-extracted from the abstract
Characteristics Experimental animal study Peer reviewed
Population Rats
Interventions Ketamine Dizocilpine maleate Haloperidol SCH23390 6-hydroxydopamine lesioning
Measures fimbria-evoked field potentials, paired-pulse facilitation
Topics Depression Esketamine Ketamine
Key findings Ketamine depressed fimbria-evoked field potentials in the nucleus accumbens via a presynaptic, NMDA receptor-dependent mechanism that requires dopamine D2 receptor activation, supporting the theory of aberrant excitatory neurotransmission in schizophrenia.

Abstract

Noncompetitive NMDA receptor antagonists, such as ketamine, induce a transient schizophrenia-like state in healthy individuals and exacerbate psychosis in schizophrenic patients. In rodents, noncompetitive NMDA receptor antagonists induce a behavioral syndrome that represents an experimentally valid model of schizophrenia. Current experimental evidence has implicated the nucleus accumbens in the pathophysiology of schizophrenia and the psychomimetic actions of ketamine. In this study, we have demonstrated that acute systemic administration of ketamine, at a dose known to produce hyperlocomotion and stereotypy, depressed the amplitude of the monosynaptic component of fimbria-evoked field potentials recorded in the nucleus accumbens. A similar effect was observed using the more selective antagonist dizocilpine maleate, indicating the depression was NMDA receptor dependent. Paired-pulse facilitation was enhanced concomitantly with, and in proportion to, ketamine-induced depressed synaptic efficacy, indicative of a presynaptic mechanism of action. Notably, the depression of field potentials recorded in the nucleus accumbens was markedly reduced after a focal 6-hydroxydopamine lesioning procedure in the nucleus accumbens. More specifically, pretreatment with the D2/D4antagonist haloperidol, but not the D1antagonistSCH23390, blocked ketamine-induced depression of nucleus accumbens responses. Our findings provide supporting evidence for the contemporary theory of schizophrenia as aberrant excitatory neurotransmission at the level of the nucleus accumbens.

Comparable studies

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

Study Year Design Participants
Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats 2020 Preclinical study
A Single Subanesthetic Dose of Ketamine Relieves Depression-like Behaviors Induced by Neuropathic Pain in Rats Rats with spared nerve injury (neuropathic pain model), sham-operated rats, and control... 2011 Animal experimental study
Comparison of (R)-ketamine and lanicemine on depression-like phenotype and abnormal composition of gut microbiota in a social defeat stress model Susceptible mice after chronic social defeat stress 2017 Preclinical animal study
Comparison of R-ketamine and rapastinel antidepressant effects in the social defeat stress model of depression Susceptible mice in the social defeat stress model 2016 Animal experimental study
Ketamine and its metabolite, (2R,6R)-HNK, restore hippocampal LTP and long-term spatial memory in the Wistar-Kyoto rat model of depression Wistar-Kyoto (WKY) rats and Wistar control rats 2020 Preclinical study

Citations in the library

Cited by 7

and 2 more in the library

Cites 5

Related reading

Explore topics

Depression Esketamine Ketamine Addiction

By condition and practice

Ketamine for depression