Effects of capsaicin, a TRPV1 channel agonist, on ketamine-induced psychosis in a mouse model of schizophrenia

Abstract

Schizophrenia is a prevalent and challenging psychiatric disorder with limited treatment options due to drug resistance and adverse effects. Emerging evidence suggests a potential role of TRPV1 channels in schizophrenia pathology, associated with disrupted thermoregulation and altered pain responses. This study investigates the effects of capsaicin, a TRPV1 channel agonist, on memory and motor impairments in a ketamine-induced mouse model of schizophrenia. Male C57BL/6 mice received a single intraperitoneal injection of ketamine (10 mg/kg) to induce psychosis-like behaviors. Capsaicin (0.1, 1, and 3 mg/kg, I.P.) was administered 30 minutes before ketamine. Behavioral assessments included the novel object recognition test (NORT) and Y-maze test for memory deficits and the open-field test for locomotor activity. Rearing and grooming were considered stereotypic behaviors. Risperidone (0.5 mg/kg, I.P.) served as the positive control. Capsaicin at 3 mg/kg significantly ameliorated ketamine-induced deficits in object exploration time and spontaneous alternation behaviors, while lower doses were ineffective. Additionally, capsaicin reduced ketamine-induced stereotypical grooming and rearing behaviors. These findings suggest that TRPV1 agonism mitigates ketamine-induced cognitive and motor impairments, highlighting TRPV1 channels as potential therapeutic targets in schizophrenia.

Keywords

• Ketamine
• capsaicin
• schizophrenia
• TRPV1 protein
• rat

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