The default mode network (DMN) is a central, large-scale brain network implicated in a range of cognitive functions and neuropsychiatric disorders, such as major depressive disorder (MDD). Studying the DMN's complex dynamics in animal models provides invaluable insights into its function in both healthy and pathological states. However, performing stable, long-term, large-scale...
Diverse antidepressants were recently described to bind to TrkB (tyrosine kinase B) and drive a positive allosteric modulation of endogenous BDNF (brain-derived neurotrophic factor). Although neurotrophins such as BDNF can bind to p75NTR (p75 neurotrophin receptor), their precursors are the high-affinity p75NTR ligands. While part of an unrelated receptor family capable of inducing completely...
Antidepressant drugs promote neuronal plasticity, and activation of brain-derived neurotrophic factor (BDNF) signaling through its receptor neuronal receptor tyrosine kinase 2 (NTRK2 or TRKB) is among the critical steps in this process. These mechanisms are shared by typical slow-acting antidepressants, fast-acting ketamine, and psychedelic compounds, although the cellular targets of each drug...
We begin by summarizing several examples of antidepressants whose therapeutic actions begin when they encounter their targets in the cytoplasm or in the lumen of an organelle. These actions contrast with the prevailing view that most neuropharmacological actions begin when drugs engage their therapeutic targets at extracellular binding sites of plasma membrane targets-ion channels, receptors,...
Classical psychedelic drugs, e.g., psilocybin and LSD, stimulate the serotonin 2A receptor (5-HT2AR) and have recently been intensely investigated for their clinical effects in various brain disorders. At the ECNP "New Frontiers meeting" in March 2023, scientific experts in psychedelics met to identify key knowledge gaps in the mechanism of action of psychedelics as investigated using...
Serotonergic psychedelics, such as psilocybin and LSD, have garnered significant attention in recent years for their potential therapeutic effects and unique mechanisms of action. These compounds exert their primary effects through activating serotonin 5-HT2A receptors, found predominantly in cortical regions. By interacting with these receptors, serotonergic psychedelics induce alterations in...
Abstract Psychedelics produce fast and persistent antidepressant effects and induce neuroplasticity resembling the effects of clinically approved antidepressants. We recently reported that pharmacologically diverse antidepressants, including fluoxetine and ketamine, act by binding to TrkB, the receptor for BDNF. Here we show that lysergic acid diethylamide (LSD) and psilocin directly bind to...
Ketamine has been described as a fast‐acting antidepressant, exerting effects in depressed patients and in preclinical models with a rapid onset of action. The typical antidepressant fluoxetine is known to induce plasticity in the adult rodent visual cortex, as assessed by a shift in ocular dominance, a classical model of brain plasticity, and a similar effect has been described for ketamine...
Psychedelic drugs have reemerged as tools to treat several brain disorders. Cultural attitudes toward them are changing, and scientists are once again investigating the neural mechanisms through which these drugs impact brain function. The significance of this research direction is reflected by recent work, including work presented by these authors at the 2022 meeting of the Society for...
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....
Brain-derived neurotrophic factor (BDNF) is involved in synaptic development and plasticity, and alterations in BDNF expression or signaling are implicated in drug addiction and psychiatric diseases, such as depression and schizophrenia. In this study, we administered phencyclidine to postnatal and adult rats with different time schedules, and determined the correlations between BDNF expression...