Cannabidiol Modulates the Motor Profile and NMDA Receptor-related Alterations Induced by Ketamine

Brakatselos, Charalampos; Delis, Foteini; Asprogerakas, M.Z.; Lekkas, Panagiotis; Tseti, Ioulia; Tzimas, Petros S.; Petrakis, Eleftherios A.; Halabalaki, Maria; Skaltsounis, Léandros; Αντωνίου, Κατερίνα

doi:10.1016/j.neuroscience.2020.09.029

Cited by 10 publications

(18 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, ERK1/2 phosphorylation does not follow the expression pattern of NMDA subunits in all brain regions. Moreover in our previous report, we showed that after acute KET administration, p-ERK1/2 levels decreased only in the NAc, while GluN2B levels decreased in both the NAc and the VH (Brakatselos et al, 2021). Based on our findings, it could be suggested that the chronic KET-induced increase in the glutamate receptor subunit expression could be linked to enhanced ERK1/2 signaling, and interestingly, CBD modulates this effect in a region-specific manner.…”

Section: Discussionsupporting

confidence: 67%

“…Ketamine (Ketamidor ® ) was dissolved in saline (0.9%NaCl, sterile). CBD (>99% pure) was prepared according to previously established protocols (Brakatselos et al, 2021;Tzimas et al, 2021). CBD was isolated from fiber-type C. sativa inflorescences of an EU-approved variety ('Futura 75').…”

Section: Drugsmentioning

confidence: 99%

“…The selected dose of KET (30 mg/kg) was based on our pilot experiments and previous studies which have shown that this dose is the appropriate for KET-induced schizophrenia-like model (Becker et al, 2003;Becker et al, 2009;Nikiforuk and Popik 2012;Kozela et al, 2020). CBD dose was selected based on our acute studies (Brakatselos et al, 2021), and our preliminary data which are in line with a recent study where CBD counteracted repeated KET (30 mg/kg)-induced effects on cognitive functions and transcriptomic alterations (Kozela et al, 2020). Moreover, the duration of the wash-out periods was chosen based on the aforementioned studies, and reports regarding KET (Zanos et al, 2018) and CBD (Hložek et al, 2017) pharmacokinetic properties.…”

Section: Ketamine-induced Activity Profile and Cannabidiol Potential Counteracting Rolementioning

confidence: 99%

“…Ketamine (KET) has been extensively used as an anesthetic, analgesic, and recently as an antidepressant, whereas each of the aforementioned indications has been related to a distinct dose range ( Nowacka and Borczyk, 2019 ). Moreover, clinical and preclinical studies have shown the psychotomimetic KET-induced profile ( Duncan et al, 1998 ; Georgiadou et al, 2014 ; Brakatselos et al, 2021 ) and, as a result, acute and chronic sub-anesthetic KET administration has been widely used to model psychosis and schizophrenia-like symptomatology and pathophysiology ( Malhotra et al, 1997 ; Lahti et al, 2001 ; Becker et al, 2003 ; Nikiforuk and Popik, 2012 ; Beck et al, 2020 ; Kozela et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…Post-mortem findings from patients with schizophrenia, as well as preclinical studies link the disease’s biological substrate with impaired expression of glutamate receptors ( Meador-Woodruff and Healy, 2000 ; Mueller et al, 2004 ; Benesh et al, 2020 ), which, in turn, is regarded as an index of neuroplasticity ( El-Gaamouch et al, 2012 ; Brakatselos et al, 2021 ; Piva et al, 2021 ). In parallel, NMDA receptor inhibitors, including KET, have been shown to affect neuroplastic indices in a plethora of experimental models; these neuroplastic effects involve changes in the glutamate receptor status in terms of expression, subunit composition, phosphorylation state, and downstream signaling ( Anver et al, 2011 ; Kamiyama et al, 2011 ; McNally et al, 2011 ; Izumi and Zorumski, 2014 ; Widman and McMahon, 2018 ; Piva et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

CBD Effects on Motor Profile and Neurobiological Indices Related to Glutamatergic Function Induced by Repeated Ketamine Pre-Administration

et al. 2021

Self Cite

View full text Add to dashboard Cite

Clinical evidence and experimental studies have shown the psychotomimetic properties induced by ketamine. Moreover, acute or chronic ketamine (KET) administration has been widely used for modeling schizophrenia-like symptomatology and pathophysiology. Several studies have reported the antipsychotic potential of cannabidiol (CBD), while there is limited information on the cannabidiol effect on KET-induced schizophrenia-like impairments. Therefore, the goal of the present study was to evaluate neuroplastic changes induced by repeated KET administration, which is used as an experimental model of schizophrenia—with a behavioral focus on positive-like symptomatology– and to assess the modulatory role of CBD treatment. The present findings have shown a robust increase in motor activity in KET-treated rats, following a 10-day period of chronic administration at the sub-anesthetic dose of 30 mg/kg (i.p), that was reversed to normal by subsequent chronic CBD treatment. Concerning the expression of glutamate receptors, the current findings have shown region-dependent KET-induced constitutional alterations in NMDA and AMPA receptors that were modified by subsequent CBD treatment. Additionally, repeated KET administration increased ERK1/2 phosphorylation state in all regions examined, apart from the ventral hippocampus that was modulated by subsequent CBD treatment. The present results show, for the first time, a stimulated motor output coupled with a specific glutamatergic-related status and ERK1/2 activation following chronic KET administration that were attenuated by CBD treatment, in a region-dependent manner. These findings provide novel information concerning the antipsychotic potential of CBD using a specific design of chronic KET administration, thus contributing to experimental approaches that mirror the symptomatology and pathophysiology of schizophrenia.

show abstract

Section: Discussionsupporting

confidence: 67%

Section: Drugsmentioning

confidence: 99%

Section: Ketamine-induced Activity Profile and Cannabidiol Potential Counteracting Rolementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

CBD Effects on Motor Profile and Neurobiological Indices Related to Glutamatergic Function Induced by Repeated Ketamine Pre-Administration

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

Ketamine induces insomnia‐like symptom of zebrafish at environmentally relevant concentrations by mediating GABAergic synapse

Guo,

He,

Mao

et al. 2024

Environmental Toxicology

View full text Add to dashboard Cite

Although the stimulative effects on the normal behaviors of fish posed by ketamine (KET) were well‐studied, the adverse effects on the behavioral functions induced by KET at nighttime were unknown. Here, we used zebrafish larvae as a model exposed to KET (10, 50, 100, and 250 ng/L) at environmental levels for 21 days. The behavioral functions at nighttime, morphological changes during exposure stage, and alterations on the associated genes transcriptional levels of fish were determined. The difficultly initiating sleep was found in the fish exposed to KET, while the sleep duration of the animals was at the normal levels in exposure groups. The significant suppressions of the developmentally relevant genes, including bmp2, bmp4, and pth2ra were consistent with the developmental abnormalities of fish found in exposure groups. Moreover, the expression of γ‐aminobutyric acid (GABA) receptor increased and melatonin (MTN) receptor decreased while the levels of GABA and MTN remained unchanged after exposure, by gene expression analysis and molecular docking. In addition, the transcriptional expression of apoptotic genes, including tp53, aifm1, and casp6, was significantly upregulated by KET. After a 7‐day recovery, the insomnia‐like behaviors (shorter sleep duration) were observed in zebrafish from the 250 ng/L‐KET group. Accordingly, the adverse outcome pathway framework of KET was constructed by prognostic assessment of zebrafish larvae. This study suggested that the adverse outcomes of KET on the sleep health of organisms at environmentally relevant concentrations should be concerned.

show abstract

Cannabidiol as an antipsychotic drug

Fabris,

Lisboa,

Guimarães

et al. 2024

International Review of Neurobiology

View full text Add to dashboard Cite

Cannabidiol Modulates the Motor Profile and NMDA Receptor-related Alterations Induced by Ketamine

Cited by 10 publications

References 73 publications

CBD Effects on Motor Profile and Neurobiological Indices Related to Glutamatergic Function Induced by Repeated Ketamine Pre-Administration

CBD Effects on Motor Profile and Neurobiological Indices Related to Glutamatergic Function Induced by Repeated Ketamine Pre-Administration

Ketamine induces insomnia‐like symptom of zebrafish at environmentally relevant concentrations by mediating GABAergic synapse

Cannabidiol as an antipsychotic drug

Contact Info

Product

Resources

About