Nitrous oxide induces hypothermia and TrkB activation: Maintenance of body temperature abolishes antidepressant-like effects in mice.
Okko Alitalo, Samuel Kohtala, Marko Rosenholm, Roosa Saarreharju, Gemma González-Hernández, Mirkka Sarparanta, Stanislav Rozov, Tomi Rantamäki
Neuropharmacology December 15, 2024 DOI: 10.1016/j.neuropharm.2024.110172 via PubMed
Summary
AI-generated from the abstractA brief exposure to nitrous oxide (N2O) causes a drop in body temperature, reduced movement, enhanced slow-wave brain activity, decreased brain glucose use, and increased phosphorylation of TrkB, GSK3β, and p70S6K in the medial prefrontal cortex of adult male mice. Preventing the hypothermic response in a chronic stress model of depression weakened the antidepressant-like behavioral effects of N2O in the saccharin preference test. These findings indicate that N2O treatment modulates TrkB signaling and related neurotrophic pathways in a temperature-dependent manner, linking altered thermoregulation and energy expenditure to antidepressant-like behavioral responses.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Adult male mice |
| Duration | Brief exposure |
| Keywords | Glucose utilization Hypothermia Metabolism Physiology Rapid-acting antidepressant |
| Key finding | Nitrous oxide treatment modulates TrkB signaling and related neurotrophic signaling pathways in a temperature-dependent manner, and preventing hypothermia attenuates its antidepressant-like behavioral effects. |
Abstract
Recent studies indicate that nitrous oxide (N2O), a gaseous anesthetic and an NMDA (N-methyl-D-aspartate) receptor antagonist, produces rapid antidepressant effect in patients suffering from treatment-resistant depression. Our recent work implies that hypothermia and reduced energy expenditure are connected with antidepressant-induced activation of TrkB neurotrophin receptors - a key regulator of synaptic plasticity. In this study, we demonstrate that a brief exposure to N2O leads to a drop in body temperature following the treatment, which is linked to decreased locomotor activity; enhanced slow-wave electroencephalographic activity; reduced brain glucose utilization; and increased phosphorylation of TrkB, GSK3β (glycogen synthase kinase 3β), and p70S6K (a kinase downstream of mTor (mammalian target of rapamycin)) in the medial prefrontal cortex of adult male mice. Moreover, preventing the hypothermic response in a chronic corticosterone stress model of depression attenuated the antidepressant-like behavioral effects of N2O in the saccharin preference test. These findings indicate that N2O treatment modulates TrkB signaling and related neurotrophic signaling pathways in a temperature-dependent manner, suggesting that the phenomenon driving TrkB activation - altered thermoregulation and energy expenditure - is linked to antidepressant-like behavioral responses.