Mechanisms underlying ketamine-induced synaptic depression in rat hippocampus-medial prefrontal cortex pathway

Kamiyama, Hidekazu; Matsumoto, Machiko; Otani, Satoru; Kimura, Shin-ichi; Shimamura, Keiichi; Ishikawa, Shuhei; Yanagawa, Yoshiki; Togashi, Hiroko

doi:10.1016/j.neuroscience.2010.12.012

Cited by 56 publications

(40 citation statements)

References 53 publications

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“…Moreover, the deficit in mLTD provides a potential explanation for the key pathological feature of increased activity of the PFC pyramidal neurons (Jodo, 2013;Jodo et al, 2005;Suzuki et al, 2002) in PCP-treated rodent models. This selective increase in activation of PFC neurons is known to be mediated primarily by inputs from the hippocampo-PFC pathway (Jodo, 2013;Jodo et al, 2005;Kamiyama et al, 2011;Thomases et al, 2014) where LTD is reduced and induction of LTP is enhanced (Kamiyama et al, 2011;Thomases et al, 2014). Previous studies reveal that mLTD in PFC is observed when specifically stimulating the hippocampo-prefrontal pathway (Lopes-Aguiar et al, 2013;Parent et al, 2010;Wang and Yuan, 2009).…”

Section: Role Of M 1 Pam In Pcp-treated Micementioning

confidence: 99%

Potentiation of M1 Muscarinic Receptor Reverses Plasticity Deficits and Negative and Cognitive Symptoms in a Schizophrenia Mouse Model

Ghoshal

Rook

Dickerson

et al. 2015

Neuropsychopharmacol

122

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Schizophrenia patients exhibit deficits in signaling of the M 1 subtype of muscarinic acetylcholine receptor (mAChR) in the prefrontal cortex (PFC) and also display impaired cortical long-term depression (LTD). We report that selective activation of the M 1 mAChR subtype induces LTD in PFC and that this response is completely lost after repeated administration of phencyclidine (PCP), a mouse model of schizophrenia. Furthermore, discovery of a novel, systemically active M 1 positive allosteric modulator (PAM), VU0453595, allowed us to evaluate the impact of selective potentiation of M 1 on induction of LTD and behavioral deficits in PCP-treated mice. Interestingly, VU0453595 fully restored impaired LTD as well as deficits in cognitive function and social interaction in these mice. These results provide critical new insights into synaptic changes that may contribute to behavioral deficits in this mouse model and support a role for selective M 1 PAMs as a novel approach for the treatment of schizophrenia.

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Section: Role Of M 1 Pam In Pcp-treated Micementioning

confidence: 99%

Potentiation of M1 Muscarinic Receptor Reverses Plasticity Deficits and Negative and Cognitive Symptoms in a Schizophrenia Mouse Model

Ghoshal

Rook

Dickerson

et al. 2015

Neuropsychopharmacol

122

View full text Add to dashboard Cite

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“…Data also exist showing that dopamine receptor antagonists can modulate synaptic depression in vivo (Kamiyama et al, 2011), behavioral effects of ketamine in the forced-swim assay (Li et al, 2015), and in preclinical models predicting subjective effects of NMDA receptor blockade (Beardsley and Balster, 1988). It must be remembered, however, that the dopaminergic hypothesis as a guide to the clinical effects of ketamine and related drugs has not been not fully realized (e.g., in the area of schizophrenia) (Moghaddam and Krystal, 2012).…”

Section: Rapidly Acting Antidepressant Actions Of Ly341495mentioning

confidence: 99%

The Rapidly Acting Antidepressant Ketamine and the mGlu2/3 Receptor Antagonist LY341495 Rapidly Engage Dopaminergic Mood Circuits

Witkin

Monn

Schoepp

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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Ketamine is a rapidly acting antidepressant in patients with treatment-resistant depression (TRD). Although the mechanisms underlying these effects are not fully established, inquiry to date has focused on the triggering of synaptogenesis transduction pathways via glutamatergic mechanisms. Preclinical data suggest that blockade of metabotropic glutamate (mGlu2/3) receptors shares many overlapping features and mechanisms with ketamine and may also provide rapid efficacy for TRD patients. Central dopamine circuitry is recognized as an end target for mood regulation and hedonic valuation and yet has been largely neglected in mechanistic studies of antidepressant-relevant effects of ketamine. Herein, we evaluated the changes in dopaminergic neurotransmission after acute administration of ketamine and the mGlu2/3 receptor antagonist LY341495 [(2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid ] in preclinical models using electrophysiologic, neurochemical, and behavioral endpoints. When given acutely, both ketamine and LY341495, but not the selective serotonin reuptake inhibitor (SSRI) citalopram, increased the number of spontaneously active dopamine neurons in the ventral tegmental area (VTA), increased extracellular levels of dopamine in the nucleus accumbens and prefrontal cortex, and enhanced the locomotor stimulatory effects of the dopamine D 2/3 receptor agonist quinpirole. Further, both ketamine and LY341495 reduced immobility time in the tail-suspension assay in CD1 mice, which are relatively resistant to SSRI antidepressants. Both the VTA neuronal activation and the antidepressant phenotype induced by ketamine and LY341495 were attenuated by the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-(9CI)-benzo[f]quinoxaline-7-sulfonamide, indicating AMPA-dependent effects. These findings provide another overlapping mechanism of action of ketamine and mGlu2/3 receptor antagonism that differentiates them from conventional antidepressants and thus support the potential rapidly acting antidepressant actions of mGlu2/3 receptor antagonism in patients.

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“…The available evidence suggests that ketamine, at both sub anaesthetic and anaesthetic concentrations, influences the release of a number of neurotransmitters including acetylcholine (Nelson, Burk, Bruno, and Sarter, 2002), histamine (Fell et al, 2010), serotonin (Lindefors, Barati, and O"Connor, 1999), and norepinephrine (Kubota et al, 1999). Ketamine is also capable of promoting a dose-dependent increase in extracellular levels of dopamine within the medial prefrontal cortex (Kamiyama et al, 2011). Such findings are relevant in to our results as the 5-mg/kg rats performed worse than the 40-mg/kg rats on elements of the easy place learning task.…”

Section: Discussionmentioning

confidence: 99%

A Neuropsychological Assessment of the Effects of Chronic Ketamine Exposure in a Rodent Model of Drug Abuse

Compton¹,

Wedge²,

Poulton³

2013

LSMR

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Abstract-While used as paediatric and veterinary anaesthetic and for pain management, the nonselective NMDA (N-methyl-Daspartate) antagonist ketamine also remains popular among recreational users. As such, there is legitimate concern about the psychological and physiological consequences associated with chronic abuse of this drug. The purpose of the present investigation was to assess the impact of chronic exposure to ketamine following a period of abstinence in a rodent model of ketamine abuse. In the present experiment, rats were given repeated injections of saline, 5 mg/kg, or 40 mg/kg of ketamine. Beginning at 111 days of age, the animals were tested for retention of an aversive outcome on a step-down avoidance task and assessed for general levels of activity. In addition, the animals were trained on a series of tasks with spatial components of various levels of difficulty, a spatial learning set task, and a nonspatial response learning task. On early trials with water maze tasks of varying difficulty, the ketamine-treated rats were impaired relative to controls, with dose-dependent effects observed on many of the tasks. On probe trials the drug-treated animals spent significantly less time in the target quadrant. In addition, the performance of the drug-treated rats was inferior to that of the control animals on a spatial learning set task, and a response learning task suggesting some difficulty in adapting their responses to changing task demands. The results suggest that chronic exposure to this NMDA receptor antagonist in young adult rats is capable of producing a variety of changes that affect nonspatial learning and memory performance in adulthood, well after the drug exposure period.

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Mechanisms underlying ketamine-induced synaptic depression in rat hippocampus-medial prefrontal cortex pathway

Cited by 56 publications

References 53 publications

Potentiation of M1 Muscarinic Receptor Reverses Plasticity Deficits and Negative and Cognitive Symptoms in a Schizophrenia Mouse Model

Potentiation of M1 Muscarinic Receptor Reverses Plasticity Deficits and Negative and Cognitive Symptoms in a Schizophrenia Mouse Model

The Rapidly Acting Antidepressant Ketamine and the mGlu2/3 Receptor Antagonist LY341495 Rapidly Engage Dopaminergic Mood Circuits

A Neuropsychological Assessment of the Effects of Chronic Ketamine Exposure in a Rodent Model of Drug Abuse

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