Effects of beta-hydroxybutyrate administration on MK-801-induced schizophrenia-like behaviour in mice

Ann Katrin Kraeuter, Tadiwa Mashavave, Aditya Suvarna, Maarten van den Buuse, Zoltán Sarnyai

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Rationale: Impaired cerebral glucose metabolism is a core pathological feature of schizophrenia. We recently demonstrated that a ketogenic diet, causing a shift from glycolysis to ketosis, normalized schizophrenia-like behaviours in an acute N-methyl-D-aspartate (NMDA) receptor antagonist model of the illness. Ketogenic diet produces the ketone body, β-hydroxybutyrate (BHB), which may serve as an alternative fuel source in its own right without a strict dietary regime. Objective: We hypothesized that chronic administration of BHB replicates the therapeutic effects of ketogenic diet in an acute NMDA receptor hypofunction model of schizophrenia in mice. Methods: C57Bl/6 mice were either treated with acute doses of 2 mmol/kg, 10 mmol/kg, or 20 mmol/kg BHB or received daily intraperitoneal injections of 2 mmol/kg BHB or saline for 3 weeks. Behavioural testing assessed the effect of acute challenge with 0.2 mg/kg MK-801 or saline on open field behaviour, social interaction, and prepulse inhibition of startle (PPI). Results: Acute BHB administration dose-dependently increased BHB plasma levels, whereas the 2 mmol/kg dose increased plasma glucose levels. The highest acute dose of BHB supressed spontaneous locomotor activity, MK-801-induced locomotor hyperactivity and MK-801-induced disruption of PPI. Chronic BHB treatment normalized MK-801-induced hyperlocomotion, reduction of sociability, and disruption of PPI. Conclusion: In conclusion, BHB may present a novel treatment option for patients with schizophrenia by providing an alternative fuel source to normalize impaired glucose metabolism in the brain.
Original languageEnglish
Pages (from-to)1397-1405
Number of pages9
JournalPsychopharmacology
Volume237
Issue number5
Early online date28 Jan 2020
DOIs
Publication statusPublished - 1 May 2020
Externally publishedYes

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