Cannabidiol reverses myeloperoxidase hyperactivity in the prefrontal cortex and striatum, and reduces protein carbonyls in the hippocampus in a ketamine-induced schizophrenia rat model

Sofia de Almeida Queiroz; Linério Ribeiro de Novais Junior; Anita Beatriz Pacheco de Carvalho; Tiago Vicente da Silva; Suelen de Souza Ramos; Vicente Meneguzzo; Khiany Mathias; Anita Dal Bó Tiscoski; Natália Piacentini; Mariana Pereira de Souza Goldim; Betine Pinto Moehlecke Iser; Fabricia Petronilho; Antonio Inserra; Rafael Mariano de Bitencourt

doi:10.1016/j.schres.2025.03.031

Cannabidiol reverses myeloperoxidase hyperactivity in the prefrontal cortex and striatum, and reduces protein carbonyls in the hippocampus in a ketamine-induced schizophrenia rat model

Sofia de Almeida Queiroz, Linério Ribeiro de Novais Junior, Anita Beatriz Pacheco de Carvalho, Tiago Vicente da Silva, Suelen de Souza Ramos, Vicente Meneguzzo, Khiany Mathias, Anita Dal Bó Tiscoski, Natália Piacentini, Mariana Pereira de Souza Goldim, Betine Pinto Moehlecke Iser, Fabricia Petronilho, Antonio Inserra, Rafael Mariano de Bitencourt

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

Background: Schizophrenia (SCZ) has limited treatment options, often with significant side effects. Cannabidiol (CBD), a non-euphoric phytocannabinoid, has shown potential as a novel therapeutic option in SCZ due to antipsychotic-like, anti-inflammatory, and antioxidant properties. We compared the therapeutic effects of CBD and risperidone (RISP) in a rat model of SCZ induced by sub-chronic ketamine (KET), focusing on inflammatory and oxidative stress, and behavioral phenotypes. Methods: Rats were pre-treated with KET or saline (SAL) for 10 days followed by CBD or RISP for 8 days. Locomotion, anxiety- and anhedonia-like behavior, and recognition memory were assessed. Oxidative damage as measured by protein carbonyls, thiobarbituric acid reactive substances, and catalase activity, and the inflammation markers myeloperoxidase (MPO) activity and nitrite/nitrate (N/N) concentration ratio were assessed in the prefrontal cortex (PFC), hypothalamus (HYP), hippocampus (HPC), and striatum, brain areas relevant to SCZ. Results: CBD restored the KET-induced decreased rearing behavior in the OFT, while RISP further decreased rearing. RISP treatment in control rats decreased rearing and elicited an anhedonic-like phenotype, while CBD did not. CBD, but not RISP restored the KET-induced increased levels of MPO activity in the PFC and the striatum, and protein carbonyls in the HPC. Post-KET treatment with RISP but not CBD decreased protein carbonyls in the PFC, and decreased the N/N concentration ratio in the HYP. Conclusion: CBD restored the KET-induced decrease in rearing behavior without inducing an anhedonic-like phenotype as observed with RISP. CBD, and to a lesser extent RISP restored the oxidative stress and neuroinflammation elicited by KET in the striatum, HPC, and PFC. These findings support the possibility that the antipsychotic effects of CBD might be mediated by its antioxidant and anti-inflammatory effects.

Original language	English
Pages (from-to)	82-95
Number of pages	14
Journal	SCHIZOPHRENIA RESEARCH
Volume	278
DOIs	https://doi.org/10.1016/j.schres.2025.03.031
Publication status	Published - Apr 2025
Externally published	Yes

Keywords

Cannabidiol
CBD
Ketamine
Rats
Risperidone
Schizophrenia

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de Almeida Queiroz, S., de Novais Junior, L. R., de Carvalho, A. B. P., da Silva, T. V., de Souza Ramos, S., Meneguzzo, V., Mathias, K., Tiscoski, A. D. B., Piacentini, N., de Souza Goldim, M. P., Iser, B. P. M., Petronilho, F., Inserra, A., & de Bitencourt, R. M. (2025). Cannabidiol reverses myeloperoxidase hyperactivity in the prefrontal cortex and striatum, and reduces protein carbonyls in the hippocampus in a ketamine-induced schizophrenia rat model. SCHIZOPHRENIA RESEARCH, 278, 82-95. https://doi.org/10.1016/j.schres.2025.03.031

@article{af6c07d467174ab8a30f4b9a48d7b9fb,

title = "Cannabidiol reverses myeloperoxidase hyperactivity in the prefrontal cortex and striatum, and reduces protein carbonyls in the hippocampus in a ketamine-induced schizophrenia rat model",

abstract = "Background: Schizophrenia (SCZ) has limited treatment options, often with significant side effects. Cannabidiol (CBD), a non-euphoric phytocannabinoid, has shown potential as a novel therapeutic option in SCZ due to antipsychotic-like, anti-inflammatory, and antioxidant properties. We compared the therapeutic effects of CBD and risperidone (RISP) in a rat model of SCZ induced by sub-chronic ketamine (KET), focusing on inflammatory and oxidative stress, and behavioral phenotypes. Methods: Rats were pre-treated with KET or saline (SAL) for 10 days followed by CBD or RISP for 8 days. Locomotion, anxiety- and anhedonia-like behavior, and recognition memory were assessed. Oxidative damage as measured by protein carbonyls, thiobarbituric acid reactive substances, and catalase activity, and the inflammation markers myeloperoxidase (MPO) activity and nitrite/nitrate (N/N) concentration ratio were assessed in the prefrontal cortex (PFC), hypothalamus (HYP), hippocampus (HPC), and striatum, brain areas relevant to SCZ. Results: CBD restored the KET-induced decreased rearing behavior in the OFT, while RISP further decreased rearing. RISP treatment in control rats decreased rearing and elicited an anhedonic-like phenotype, while CBD did not. CBD, but not RISP restored the KET-induced increased levels of MPO activity in the PFC and the striatum, and protein carbonyls in the HPC. Post-KET treatment with RISP but not CBD decreased protein carbonyls in the PFC, and decreased the N/N concentration ratio in the HYP. Conclusion: CBD restored the KET-induced decrease in rearing behavior without inducing an anhedonic-like phenotype as observed with RISP. CBD, and to a lesser extent RISP restored the oxidative stress and neuroinflammation elicited by KET in the striatum, HPC, and PFC. These findings support the possibility that the antipsychotic effects of CBD might be mediated by its antioxidant and anti-inflammatory effects.",

keywords = "Cannabidiol, CBD, Ketamine, Rats, Risperidone, Schizophrenia",

author = "{de Almeida Queiroz}, Sofia and {de Novais Junior}, {Lin{\'e}rio Ribeiro} and {de Carvalho}, {Anita Beatriz Pacheco} and {da Silva}, {Tiago Vicente} and {de Souza Ramos}, Suelen and Vicente Meneguzzo and Khiany Mathias and Tiscoski, {Anita Dal B{\'o}} and Nat{\'a}lia Piacentini and {de Souza Goldim}, {Mariana Pereira} and Iser, {Betine Pinto Moehlecke} and Fabricia Petronilho and Antonio Inserra and {de Bitencourt}, {Rafael Mariano}",

year = "2025",

month = apr,

doi = "10.1016/j.schres.2025.03.031",

language = "English",

volume = "278",

pages = "82--95",

journal = "SCHIZOPHRENIA RESEARCH",

issn = "0920-9964",

publisher = "Elsevier B.V.",

}

de Almeida Queiroz, S, de Novais Junior, LR, de Carvalho, ABP, da Silva, TV, de Souza Ramos, S, Meneguzzo, V, Mathias, K, Tiscoski, ADB, Piacentini, N, de Souza Goldim, MP, Iser, BPM, Petronilho, F, Inserra, A & de Bitencourt, RM 2025, 'Cannabidiol reverses myeloperoxidase hyperactivity in the prefrontal cortex and striatum, and reduces protein carbonyls in the hippocampus in a ketamine-induced schizophrenia rat model', SCHIZOPHRENIA RESEARCH, vol. 278, pp. 82-95. https://doi.org/10.1016/j.schres.2025.03.031

Cannabidiol reverses myeloperoxidase hyperactivity in the prefrontal cortex and striatum, and reduces protein carbonyls in the hippocampus in a ketamine-induced schizophrenia rat model. / de Almeida Queiroz, Sofia; de Novais Junior, Linério Ribeiro; de Carvalho, Anita Beatriz Pacheco et al.
In: SCHIZOPHRENIA RESEARCH, Vol. 278, 04.2025, p. 82-95.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Cannabidiol reverses myeloperoxidase hyperactivity in the prefrontal cortex and striatum, and reduces protein carbonyls in the hippocampus in a ketamine-induced schizophrenia rat model

AU - de Almeida Queiroz, Sofia

AU - de Novais Junior, Linério Ribeiro

AU - de Carvalho, Anita Beatriz Pacheco

AU - da Silva, Tiago Vicente

AU - de Souza Ramos, Suelen

AU - Meneguzzo, Vicente

AU - Mathias, Khiany

AU - Tiscoski, Anita Dal Bó

AU - Piacentini, Natália

AU - de Souza Goldim, Mariana Pereira

AU - Iser, Betine Pinto Moehlecke

AU - Petronilho, Fabricia

AU - Inserra, Antonio

AU - de Bitencourt, Rafael Mariano

PY - 2025/4

Y1 - 2025/4

N2 - Background: Schizophrenia (SCZ) has limited treatment options, often with significant side effects. Cannabidiol (CBD), a non-euphoric phytocannabinoid, has shown potential as a novel therapeutic option in SCZ due to antipsychotic-like, anti-inflammatory, and antioxidant properties. We compared the therapeutic effects of CBD and risperidone (RISP) in a rat model of SCZ induced by sub-chronic ketamine (KET), focusing on inflammatory and oxidative stress, and behavioral phenotypes. Methods: Rats were pre-treated with KET or saline (SAL) for 10 days followed by CBD or RISP for 8 days. Locomotion, anxiety- and anhedonia-like behavior, and recognition memory were assessed. Oxidative damage as measured by protein carbonyls, thiobarbituric acid reactive substances, and catalase activity, and the inflammation markers myeloperoxidase (MPO) activity and nitrite/nitrate (N/N) concentration ratio were assessed in the prefrontal cortex (PFC), hypothalamus (HYP), hippocampus (HPC), and striatum, brain areas relevant to SCZ. Results: CBD restored the KET-induced decreased rearing behavior in the OFT, while RISP further decreased rearing. RISP treatment in control rats decreased rearing and elicited an anhedonic-like phenotype, while CBD did not. CBD, but not RISP restored the KET-induced increased levels of MPO activity in the PFC and the striatum, and protein carbonyls in the HPC. Post-KET treatment with RISP but not CBD decreased protein carbonyls in the PFC, and decreased the N/N concentration ratio in the HYP. Conclusion: CBD restored the KET-induced decrease in rearing behavior without inducing an anhedonic-like phenotype as observed with RISP. CBD, and to a lesser extent RISP restored the oxidative stress and neuroinflammation elicited by KET in the striatum, HPC, and PFC. These findings support the possibility that the antipsychotic effects of CBD might be mediated by its antioxidant and anti-inflammatory effects.

AB - Background: Schizophrenia (SCZ) has limited treatment options, often with significant side effects. Cannabidiol (CBD), a non-euphoric phytocannabinoid, has shown potential as a novel therapeutic option in SCZ due to antipsychotic-like, anti-inflammatory, and antioxidant properties. We compared the therapeutic effects of CBD and risperidone (RISP) in a rat model of SCZ induced by sub-chronic ketamine (KET), focusing on inflammatory and oxidative stress, and behavioral phenotypes. Methods: Rats were pre-treated with KET or saline (SAL) for 10 days followed by CBD or RISP for 8 days. Locomotion, anxiety- and anhedonia-like behavior, and recognition memory were assessed. Oxidative damage as measured by protein carbonyls, thiobarbituric acid reactive substances, and catalase activity, and the inflammation markers myeloperoxidase (MPO) activity and nitrite/nitrate (N/N) concentration ratio were assessed in the prefrontal cortex (PFC), hypothalamus (HYP), hippocampus (HPC), and striatum, brain areas relevant to SCZ. Results: CBD restored the KET-induced decreased rearing behavior in the OFT, while RISP further decreased rearing. RISP treatment in control rats decreased rearing and elicited an anhedonic-like phenotype, while CBD did not. CBD, but not RISP restored the KET-induced increased levels of MPO activity in the PFC and the striatum, and protein carbonyls in the HPC. Post-KET treatment with RISP but not CBD decreased protein carbonyls in the PFC, and decreased the N/N concentration ratio in the HYP. Conclusion: CBD restored the KET-induced decrease in rearing behavior without inducing an anhedonic-like phenotype as observed with RISP. CBD, and to a lesser extent RISP restored the oxidative stress and neuroinflammation elicited by KET in the striatum, HPC, and PFC. These findings support the possibility that the antipsychotic effects of CBD might be mediated by its antioxidant and anti-inflammatory effects.

KW - Cannabidiol

KW - CBD

KW - Ketamine

KW - Rats

KW - Risperidone

KW - Schizophrenia

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U2 - 10.1016/j.schres.2025.03.031

DO - 10.1016/j.schres.2025.03.031

M3 - Article

C2 - 40132281

AN - SCOPUS:105000778872

SN - 0920-9964

VL - 278

SP - 82

EP - 95

JO - SCHIZOPHRENIA RESEARCH

JF - SCHIZOPHRENIA RESEARCH

ER -

de Almeida Queiroz S, de Novais Junior LR, de Carvalho ABP, da Silva TV, de Souza Ramos S, Meneguzzo V et al. Cannabidiol reverses myeloperoxidase hyperactivity in the prefrontal cortex and striatum, and reduces protein carbonyls in the hippocampus in a ketamine-induced schizophrenia rat model. SCHIZOPHRENIA RESEARCH. 2025 Apr;278:82-95. doi: 10.1016/j.schres.2025.03.031

Cannabidiol reverses myeloperoxidase hyperactivity in the prefrontal cortex and striatum, and reduces protein carbonyls in the hippocampus in a ketamine-induced schizophrenia rat model

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