Linagliptin, a Selective DPP-4 Inhibitor, Attenuates Ketamine- and Diazepam-Induced Deficits in Passive Avoidance Performance in Mice
Krzysztof Fronc, Piotr Listos, Paulina Kasprzak, Marcin Berger, Tymoteusz Słowik, J. Kotlinska, E. Poleszak, I. Baranowska-Bosiacka, Listos Emilia, M. Lupina, Adrian Pysiewicz, J. Listos
Brain Science June 30, 2026 DOI: 10.3390/brainsci16070710 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment (preclinical study) Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Linagliptin Ketamine Diazepam |
| Dose | Linagliptin 10 and 20 mg/kg, i.p.; ketamine 10 mg/kg, i.p.; diazepam 2 mg/kg, i.p. |
| Measures | Passive avoidance test, enzyme-linked immunosorbent assay (ELISA) |
| Topics | Esketamine Ketamine |
| Key findings | Linagliptin attenuated ketamine- and diazepam-induced deficits in passive avoidance performance in mice. Both acute and chronic linagliptin administration increased BDNF levels in the prefrontal cortex but not in the hippocampus. The authors present these as preliminary evidence and call for further studies to clarify the neuropharmacological mechanisms. |
Abstract
Highlights Linagliptin attenuated ketamine-induced passive avoidance deficits in mice. Linagliptin increased BDNF levels in the prefrontal cortex but not in the hippocampus. Abstract Background: 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.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |