Psychoneuroendocrinology. 2024 Jul 15;168:107138. doi: 10.1016/j.psyneuen.2024.107138. Online ahead of print.
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.
PMID:39068687 | DOI:10.1016/j.psyneuen.2024.107138
