Brain sciencesJul 28, 2026

Linagliptin reduces memory problems caused by ketamine and diazepam in mice

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Aug 3, 2026

Abstract

Linagliptin (10 and 20 mg/kg) attenuated deficits in passive avoidance performance induced by ketamine and diazepam in mice.

Linagliptin is a DPP-4 inhibitor that enhances GLP-1 signaling, which may influence brain function.
Mice treated with linagliptin showed improved performance in a passive avoidance test compared to those receiving ketamine or diazepam alone.
Both acute and chronic linagliptin administration increased brain-derived neurotrophic factor (BDNF) levels in the prefrontal cortex.
No increase in BDNF levels was observed in the hippocampus following linagliptin treatment.
These results suggest a potential role for linagliptin in modulating certain behavioral deficits through effects on BDNF in specific brain regions.

Simplified

Linagliptin, a potent and highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor approved for the treatment of type 2 diabetes, enhances glucagon-like peptide-1 (GLP-1) signaling. Because GLP-1 receptors are widely expressed in the brain, DPP-4 inhibitors have emerged as potential modulators of central nervous system function. The present study investigated the effects of linagliptin (10 and 20 mg/kg, i.p.) on ketamine- (10 mg/kg, i.p.) and diazepam-induced (2 mg/kg, i.p.) deficits in passive avoidance performance in mice. Behavioral effects were assessed using the passive avoidance test, and brain-derived neurotrophic factor (BDNF) levels in the prefrontal cortex and hippocampus were determined by enzyme-linked immunosorbent assay (ELISA). Linagliptin attenuated ketamine- and diazepam-induced deficits in passive avoidance performance. In addition, both acute and chronic administration of linagliptin increased BDNF levels in the prefrontal cortex but not in the hippocampus. These findings provide preliminary evidence that linagliptin modulates passive avoidance performance in mice and is associated with increased BDNF levels in the prefrontal cortex. Further studies employing complementary behavioral paradigms and additional molecular approaches are required to clarify the neuropharmacological mechanisms underlying these effects.

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Linagliptin reduces memory problems caused by ketamine and diazepam in mice

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