Behavioral effects of buspirone in a mouse model of posttraumatic stress disorder

Buspirone presents a unique profile of action, which involves activation of 5-HT_1A receptors and complex effects on D₂-like dopaminergic receptors. This medication is studied in terms of potential clinical repositioning to conditions that are associated with dopaminergic dysfunctions including schizophrenia and substance use disorder. Buspirone antagonizes D₃ and D₄ receptors, however, depending on the dose it differentially interacts with D₂ receptors. Previously, we reported that some of D₂/D₃ dopaminergic agonists attenuate PTSD-like behavioral symptoms in mice. Here we investigated whether buspirone could also affect PTSD-like symptoms. We used the single prolonged stress (mSPS) protocol to induce PTSD-like behavior in adult male CD-1 mice. Buspirone (0.5, 2, or 10 mg/kg, i.p.) was injected for 15 consecutive days. The subjects were repeatedly examined in a variety of behavioral tests measuring conditioned freezing response, antidepressant-like effects, anxiety, and ultrasonic vocal response to the restraint stress. Mouse SPS resulted in prolonged immobility in the forced swim test and freezing in the fear-conditioning test, and produced symptoms of anxiety. Buspirone dose-dependently decreased the exaggerated freezing response in mice, but only at the dose of 2 mg/kg exhibited the anxiolytic-like effect in the elevated plus maze test. Buspirone reduced the number of ultrasonic calls in mSPS-exposed mice but revealed no antidepressant-like effect in the forced swim test. Present data suggest some positive effects of buspirone in the treatment of selected PTSD-like symptoms and prompt for its further clinical evaluation.