• Modeling Mechanism：

  Dizocilpine (MK801), as a non-competitive NMDA receptor antagonist, induces schizophrenia-related pathology through NMDA receptor dysfunction: ① It disrupts the balance of excitatory/inhibitory neurotransmitters in the brain, causing dopamine system dysfunction and mimicking positive symptoms such as hallucinations and delusions; ② It inhibits normal exploratory and self-care behaviors, mimicking negative symptoms such as lack of will and emotional blunting; ③ It exhibits significant gender differences, highly consistent with the gender differences in schizophrenia symptoms (men are more likely to exhibit negative symptoms, and women are more likely to exhibit positive symptoms), providing model support for studying gender-related pathogenesis.

• Related Products：

  Dizocilpine (T6259)

• Modeling Method：

  Experimental Subject：Rats, Sprague-Dawley (SD), Male / Female (female must be oestrus-cycled), Adult (5-6 months old)

  Dosage and Administration Route：① Core modelling: Dizocilpine (0.05, 0.1, 0.2 mg/kg) dissolved in physiological saline, administered via intraperitoneal injection (to avoid gender differences caused by first-pass metabolism); ② Pre-treatment (optional): Typical antipsychotic haloperidol (0.04, 0.08 mg/kg) or atypical antipsychotic clozapine (5, 10 mg/kg), Subcutaneous injection, Administered 15 minutes prior to modelling; ③ Control treatment: equal volume saline solution administered via the same route; ④ Female rat control: Daily vaginal lavage for 10 days prior to experimentation; only rats in the proestrus phase (cyclically stable with peak oestrogen levels) selected for studies

  Dosing Frequency and Duration Model：Single dose

• Validation：

  Behavioral indicators (core validation): Positive symptom-related: - Locomotion: Females in the 0.1 and 0.2 mg/kg Dizocilpine groups showed a significant increase in locomotion frequency (P<0.001), while males only showed a significant increase in the 0.2 mg/kg group, indicating that females are more sensitive to positive symptom-related behaviors; - Stereotypy: Males in the 0.1 and 0.2 mg/kg groups showed a significant prolongation of stereotypy behaviors (head swaying, circling) duration (P<0.001), while females only showed a significant increase in the 0.2 mg/kg group; - Ataxia: Both males and females in the 0.2 mg/kg Dizocilpine group experienced frequent falls and failed standing postures, with a higher incidence in females; Negative symptom-related: - Rearing: Males in the 0.05 and 0.1 mg/kg groups showed a significant decrease in the number of standing postures (P<0.001), indicating that males are more sensitive to negative symptoms; Grooming: Grooming time was significantly shortened in males at 0.1 and 0.2 mg/kg (P<0.001), while it was slightly increased in females at 0.05 mg/kg and significantly decreased in females at 0.2 mg/kg; Stationary behavior: Stationary behavior was significantly reduced in both males and females at 0.2 mg/kg Dizocilpine (P<0.05), with a more significant reduction in females; Anxiety-related (comorbidity features): Thigmotaxis: The proportion of time spent moving against a wall was significantly increased in males at 0.1 and 0.2 mg/kg (P<0.001), while there was no significant change in females.

*Precautions： Animals were euthanized humanely in accordance with ethical requirements after the experiment. If long-term observation is required, behavioral changes should be monitored regularly, and animals exhibiting severe abnormal behavior should be euthanized promptly.

*References：Feinstein I,and Kritzer MF. Acute N-methyl-D-aspartate receptor hypofunction induced by Dizocilpine evokes sex-specific changes in behaviors observed in open-field testing in adult male and proestrus female rats. Neuroscience. 2013 Jan 3;228:200-14.