Biology of Sex Differences
July 7, 2026
Gemma González-Hernández, S. Torres-Sánchez, D. Sanchez-Morillo et al.
Chronic pain-depression comorbidity is characterized by sensory hypersensitivity and emotional dysregulation, and has been linked to alterations in prefrontal network connectivity. It represents a major therapeutic challenge due to its pronounced sex differences in symptom manifestation and increased treatment resistance. Nitrous oxide (N₂O), an inhalational anesthetic traditionally used for...
Journal of Neurophysiology
May 1, 2025
Petra Valtonen, Stanislav Rozov, Iina Annala et al.
Nitrous oxide (N2O) may elicit antidepressant effects after its elimination from the brain. We sought to investigate whether short-term administration of N2O triggers power within the delta (0.5-4 Hz) and/or theta (4-7 Hz) frequency ranges in the electroencephalogram (EEG) after it's administration, as we have recently seen such rebound effects to N2O in studies conducted on mice. Twenty...
Neuropharmacology
December 15, 2024
Okko Alitalo, Samuel Kohtala, Marko Rosenholm et al.
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...
Nature Communications
August 23, 2024
David H. Sarrazin, Wilf Gardner, Carole Marchese et al.
41 citations
Depression is associated with dysregulated circadian rhythms, but the role of intrinsic clocks in mood-controlling brain regions remains poorly understood. We found increased circadian negative loop and decreased positive clock regulators expression in the medial prefrontal cortex (mPFC) of a mouse model of depression, and a subsequent clock countermodulation by the rapid antidepressant...
European Journal of Pharmacology
April 5, 2024
Stanislav Rozov, Roosa Saarreharju, Stanislav Khirug et al.
Nitrous oxide (N2O; laughing gas) has recently reported to produce rapid antidepressant effects, but little is known about the underlying mechanisms. We performed transcriptomics, in situ hybridization, and electrophysiological studies to examine the potential shared signatures induced by 1 h inhalation of 50% N2O and a single subanesthetic dose of ketamine (10 mg/kg, i.p.) in the medial...
bioRxiv Preprint Server
September 19, 2022
Stanislav Rozov, Roosa Saarreharju, Stanislav Khirug et al.
preprint
Nitrous oxide (N2O; laughing gas) has recently been reported as a putative rapid-acting antidepressant, but little is known about the underlying mechanisms. We performed transcriptomics, in situ hybridization, and electrophysiological studies to examine the potential shared signatures induced by 1 h inhalation of 50% N2O and a single subanesthetic dose of ketamine in the medial prefrontal...
bioRxiv
August 31, 2021
Okko Alitalo, Samuel Kohtala, Marko Rosenholm et al.
preprint
We show that both pharmacological and non-pharmacological treatments of depression activate TrkB receptors—a well-established target of antidepressants—by inducing a physiological response coupled to sedation. Several rapid-acting antidepressants trigger TrkB signaling by evoking a state associated with electroencephalographic slow-wave activity, behavioral immobility, reduced cerebral glucose...
Basic & Clinical Pharmacology & Toxicology
August 1, 2021
Samuel Kohtala, Tomi Rantamäki
Increased glutamatergic neurotransmission and synaptic plasticity in the prefrontal cortex have been associated with the rapid antidepressant effects of ketamine. Activation of BDNF (brain-derived neurotrophic factor) receptor TrkB is considered a key molecular event for antidepressant-induced functional and structural synaptic plasticity. Several mechanisms have been proposed to underlie...
Progress in Neuro-psychopharmacology and Biological Psychiatry
February 25, 2020
Muris Humo, Beyza Ayazgök, Léa J. Becker et al.
Chronic pain produces psychologic distress, which often leads to mood disorders such as depression. Co-existing chronic pain and depression pose a serious socio-economic burden and result in disability affecting millions individuals, which urges the development of treatment strategies targeting this comorbidity. Ketamine, a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) receptor,...
Neuropharmacology
October 1, 2019
Samuel Kohtala, Wiebke Theilmann, Marko Rosenholm et al.
Subanesthetic rather than anesthetic doses are thought to bring the rapid antidepressant effects of the NMDAR (N-methyl-d-aspartate receptor) antagonist ketamine. Among molecular mechanisms, activation of BDNF receptor TrkB along with the inhibition of GSK3β (glycogen synthase kinase 3β) are considered as critical molecular level determinants for ketamine's antidepressant effects....
Cell and tissue research
July 1, 2019
Tomi Rantamäki
The role of brain-derived neurotrophic factor (BDNF) and its receptor TrkB has been studied in the context of mood disorders and their treatments for a couple of decades. Pharmacologically diverse antidepressant drugs increase the synthesis of BDNF in the cortex (and some subcortical structures) and this effect accounts for their ability to facilitate neurotrophic processes eventually leading...
Molecular Neurobiology
June 1, 2019
Samuel Kohtala, Wiebke Theilmann, Marko Rosenholm et al.
Rapid antidepressant effects of ketamine become most evident when its psychotomimetic effects subside, but the neurobiological basis of this "lag" remains unclear. Laughing gas (N2O), another NMDA-R (N-methyl-D-aspartate receptor) blocker, has been reported to bring antidepressant effects rapidly upon drug discontinuation. We took advantage of the exceptional pharmacokinetic properties of N2O...
Neuropharmacology
January 2012
Jesse S O Lindholm, Henri Autio, Liisa Vesa et al.
Accumulating evidence suggests that biogenic amine-based antidepressants act, at least in part, via regulation of brain-derived neurotrophic factor (BDNF) signaling. Biogenic amine-based antidepressants increase BDNF synthesis and activate its signaling pathway through TrkB receptors. Moreover, the antidepressant-like effects of these molecules are abolished in BDNF deficient mice....
Samuel Kohtala, Wiebke Theilmann, Marko Rosenholm et al.
preprint
Abstract Electroconvulsive therapy (ECT) remains among the most efficient antidepressants but it seldom brings immediate remedy. However, a subanesthetic dose of NMDA-R (N-methyl-D-aspartate receptor) blocker ketamine ameliorates symptoms of depression already within hours. Glutamatergic excitability and regulation of TrkB neurotrophin receptor and GSK3β (glycogen synthase kinase 3β) signaling...