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...
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...
Pharmacological Reports
February 20, 2021
Samuel Kohtala
Over the past 50 years, ketamine has solidified its position in both human and veterinary medicine as an important anesthetic with many uses. More recently, ketamine has been studied and used for several new indications, ranging from chronic pain to drug addiction and post-traumatic stress disorder. The discovery of the rapid-acting antidepressant effects of ketamine has resulted in a surge of...
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....
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...
Samuel Kohtala, Puja K Parekh, Iman Baramaki et al.
preprint
Summary Emerging evidence suggests that nitrous oxide (N 2 O), a gaseous NMDA receptor antagonist and dissociative anesthetic, exerts rapid antidepressant effects akin to subanesthetic ketamine. However, its cellular, molecular, and behavioral effects remain poorly understood. Using in vivo two-photon imaging through cortical microprisms, we demonstrate that 50% N 2 O/O 2 rapidly increases...
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...