Chronic intranasal oxytocin alleviates cognitive impairment and reverses oxytocin signaling upregulation in MK801-induced mice

Abstract

Objective

Cognitive impairment, especially impaired social cognition, is largely responsible for the deterioration of the social life of patients with schizophrenia (SZ). Oxytocin (OT) is a neuropeptide that offers promising therapy for SZ. This study aimed to explore whether OT could affect dizocilpine (MK801)-induced cognitive impairment and to investigate the effect of exogenous OT on the endogenous OT system in the hippocampus.

Methods

The SZ mouse model was established by repeated administration of dizocilpine [MK801, 0.6 mg/kg, intraperitoneal (i.p.)], and then OT (6–60 μg/kg, intranasal) or risperidone (0.3 mg/kg, i.p.) was administered to explore the effect of OT on cognitive impairment.

Results

OT at a dose of 6 μg/kg alleviated MK801-induced hyperactivity, sociability impairment, and spatial memory impairment. OT at a dose of 20 or 60 μg/kg attenuated the hyperactivity and social novelty impairment. In MK801-injected mice, the compensatory upregulation of OT mRNA in the hippocampus was reversed by three OT doses, whereas 60 μg/kg OT reversed the compensatory upregulation of CD38 protein expression.

Conclusion

OT alleviated cognitive impairment in the SZ mouse model to varying degrees, reversing the compensatory upregulation of OT signaling in the hippocampus.