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 GAD₆₇, 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.

精神分裂症是一种慢性、使人衰弱的精神疾病，目前尚未被完全了解。在这项研究中，我们旨在研究不同剂量的氯胺酮（一种非竞争性 NMDA 受体拮抗剂）对精神分裂症阳性和阴性症状的影响。_{我们还探讨了这些影响是否与大脑结构中 GAD 67}、TH 和 PPAR-γ免疫反应性的变化有关。为了进行这项研究，雄性小鼠连续 14 天腹膜内注射氯胺酮 (20-40 mg/kg) 或其载体 (0.9% NaCl)。我们量化了刻板行为、强迫游泳测试 (FST) 中不动的时间以及 7 或 14 天后的运动活动。此外，我们对14 天后脑组织中 GAD、TH 和 PPAR-γ 的免疫反应性进行了离体分析。结果表明，在所有测试剂量下，服用氯胺酮 14 天都增加了鼻子区域的梳理时间。在 30 mg/kg 剂量下，它还增加了 FST 的不动性，并在 40 mg/kg 剂量下减少了定型行为期间的饲养周期数。这些行为影响与运动活动的变化无关。我们没有观察到脑蛋白免疫反应性的任何显着变化。然而，我们发现，在剂量为 20 和 30 mg/kg 氯胺酮时，GAD 和 TH 分别与刻板行为期间的饲养次数呈正相关。在20mg/kg剂量下，GAD与旷场试验中的饲养次数呈正相关。在剂量为 30 mg/kg 时，TH 与 FST 中的不动时间呈负相关。在氯胺酮剂量为 40 mg/kg 时，PPAR-γ 与刻板行为发作次数呈负相关。总之，氯胺酮在阳性症状中诱导的行为改变在所有测试剂量中均得到重现，并且似乎取决于 TH、GAD 和 PPAR-γ 的调节作用。相反，阴性症状与特定剂量的氯胺酮有关。