Influence of the dose of ketamine used on schizophrenia-like symptoms in mice: A correlation study with TH, GAD 67 , and PPAR-γ.

Autor: Rodrigues T; Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, RS, Brazil., Bressan GN; Programa de Pós-Graduação em Ciências Biológicas, Bioquímica Toxicológica, Universidade Federal de Santa Maria, RS, Brazil., Krum BN; Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, RS, Brazil., Soares FAA; Programa de Pós-Graduação em Ciências Biológicas, Bioquímica Toxicológica, Universidade Federal de Santa Maria, RS, Brazil., Fachinetto R; Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, RS, Brazil; Programa de Pós-Graduação em Ciências Biológicas, Bioquímica Toxicológica, Universidade Federal de Santa Maria, RS, Brazil. Electronic address: roselei.fachinetto@ufsm.br.
Jazyk: angličtina
Zdroj: Pharmacology, biochemistry, and behavior [Pharmacol Biochem Behav] 2023 Dec; Vol. 233, pp. 173658. Date of Electronic Publication: 2023 Oct 05.
DOI: 10.1016/j.pbb.2023.173658
Abstrakt: Schizophrenia is a chronic, debilitating mental illness that has not yet been completely understood. In this study, we aimed to investigate the effects of different doses of ketamine, a non-competitive NMDA receptor antagonist, on the positive- and negative-like symptoms of schizophrenia. We also explored whether these effects are related to changes in the immunoreactivity of GAD 67 , TH, and PPAR-γ in brain structures. To conduct the study, male mice received ketamine (20-40 mg/kg) or its vehicle (0.9 % NaCl) intraperitoneally for 14 consecutive days. We quantified stereotyped behavior, the time of immobility in the forced swimming test (FST), and locomotor activity after 7 or 14 days. In addition, we performed ex vivo analysis of the immunoreactivity of GAD, TH, and PPAR-γ, in brain tissues after 14 days. The results showed that ketamine administration for 14 days increased the grooming time in the nose region at all tested doses. It also increased immobility in the FST at 30 mg/kg doses and decreased the number of rearing cycles during stereotyped behavior at 40 mg/kg. These behavioral effects were not associated with changes in locomotor activity. We did not observe any significant alterations regarding the immunoreactivity of brain proteins. However, we found that GAD and TH were positively correlated with the number of rearing during the stereotyped behavior at doses of 20 and 30 mg/kg ketamine, respectively. GAD was positively correlated with the number of rearing in the open field test at a dose of 20 mg/kg. TH was inversely correlated with immobility time in the FST at a dose of 30 mg/kg. PPAR-γ was inversely correlated with the number of bouts of stereotyped behavior at a dose of 40 mg/kg of ketamine. In conclusion, the behavioral alterations induced by ketamine in positive-like symptoms were reproduced with all doses tested and appear to depend on the modulatory effects of TH, GAD, and PPAR-γ. Conversely, negative-like symptoms were associated with a specific dose of ketamine.
Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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