PT  - JOURNAL ARTICLE
AU  - Hernández-Frausto, Melissa
AU  - Galván, Emilio J
AU  - López-Rubalcava, Carolina
TI  - D1-like receptor activation rescues hippocampal synaptic plasticity and cognitive impairments in the MK-801 schizophrenia model
AID  - 10.1101/2024.06.19.599791
DP  - 2024 Jan 01
TA  - bioRxiv
PG  - 2024.06.19.599791
4099  - http://biorxiv.org/content/early/2024/06/23/2024.06.19.599791.short
4100  - http://biorxiv.org/content/early/2024/06/23/2024.06.19.599791.full
AB  - Schizophrenia is a disorder with a higher cognitive decline in early adulthood, causing impaired retention of episodic memories. However, the physiological and behavioral functions that underlie cognitive deficits with a potential mechanism to ameliorate and improve cognitive performance are unknown. In this study, we used the MK-801 neurodevelopmental schizophrenia-like model. Rats were divided into two groups: one received MK-801, and the other received saline for five consecutive days (7-11 postnatal days, PND). Using extracellular field recordings in acute hippocampal slices and the Barnes maze task, we evaluated synaptic plasticity late-LTP and spatial memory in freely moving animals in early adolescence and young adulthood. Next, we examined D1-like activation as a mechanism to ameliorate cognitive impairments. Our results suggest that MK-801 neonatal treatment induces impairment in late-LTP expression and deficits in spatial memory retrieval in early adolescence that is maintained until young adulthood. Furthermore, we found that activation of D1-like dopamine receptors ameliorates the impairments and promotes a robust expression of late-LTP and an improved performance in the Barnes maze task, suggesting a novel and potential therapeutic role in treating cognitive impairments in schizophrenia.Highlights- MK-801 Schizophrenia model induces impairment in Late-LTP at early adolescence and young developmental stage.- Barnes maze recall phase is impaired in the MK-801 Schizophrenia model.- The activation of D1-like receptors promotes recovery and induction of the- Late-LTP in the MK-801 schizophrenia model in adolescent and young adult rats.- Activation of D1-like dopamine receptors improves behavioral performance in the MK-801 schizophrenia model in adolescent and young adult rats.Graphical AbstractDisturbances in episodic memories are observed in patients with schizophrenia and rodent models. Still, the hippocampal physiological substrates with a potential rescue mechanism related to consolidation of memories have not been elucidated. Here, in vitro electrophysiology and in vivo Barnes maze task are used at two ages in the MK-801 neurodevelopmental schizophrenia-like model. We observed a loss of hippocampal late-LTP and impaired recall phase, and the activation of dopamine D1-like receptors attenuated the impairments with a rescue of both late-LTP and recall phase, suggesting an important role of D1-like receptors activity for episodic memory in schizophrenia.Competing Interest StatementThe authors have declared no competing interest.