Serotonin: A Tale of Two Receptors (5-HT1A & 5-HT2A)(II)

Описание: This 7‑min micro‑lecture explores the bipartite model of serotonin function, a framework proposing that serotonin supports two fundamentally different adaptive responses to adversity. We will use Carhart‑Harris & Nutt’s 2017 publication "Serotonin and brain function: a tale of two receptors" as our guide (full citation below).

The lecture examines how the 5‑HT1A receptor pathway promotes passive coping — a mode characterized by stress tolerance, patience, and emotional moderation. This pathway is the primary target of conventional antidepressants such as SSRIs, which enhance the brain’s ability to endure and stabilize during prolonged stress.

In contrast, the 5‑HT2A receptor pathway supports active coping by increasing neural plasticity and environmental sensitivity. Activation of this system allows for major cognitive or behavioral shifts, making it especially relevant during periods of crisis when change, rather than endurance, is the adaptive response. Psychedelics strongly activate this pathway, offering a mechanistic explanation for their capacity to facilitate psychological flexibility.

By distinguishing these two systems, the bipartite model helps clarify why serotonin can produce such diverse — and sometimes opposing — effects on mood, cognition, and behavior. Ultimately, the authors argue that serotonin equips the brain with the ability to either withstand adversity or transform in response to it, depending on which receptor system is engaged.

---

SCIENTIFIC ABSTRACT: Previous attempts to identify a unified theory of brain serotonin function have largely failed to achieve consensus. In this present synthesis, we integrate previous perspectives with new and older data to create a novel bipartite model centred on the view that serotonin neurotransmission enhances two distinct adaptive responses to adversity, mediated in large part by its two most prevalent and researched brain receptors: the 5-HT1A and 5-HT2A receptors. We propose that passive coping (i.e. tolerating a source of stress) is mediated by postsynaptic 5-HT1AR signalling and characterised by stress moderation. Conversely, we argue that active coping (i.e. actively addressing a source of stress) is mediated by 5-HT2AR signalling and characterised by enhanced plasticity (defined as capacity for change). We propose that 5-HT1AR-mediated stress moderation may be the brain's default response to adversity but that an improved ability to change one's situation and/or relationship to it via 5-HT2AR-mediated plasticity may also be important - and increasingly so as the level of adversity reaches a critical point. We propose that the 5-HT1AR pathway is enhanced by conventional 5-HT reuptake blocking antidepressants such as the selective serotonin reuptake inhibitors (SSRIs), whereas the 5-HT2AR pathway is enhanced by 5-HT2AR-agonist psychedelics. This bipartite model purports to explain how different drugs (SSRIs and psychedelics) that modulate the serotonergic system in different ways, can achieve complementary adaptive and potentially therapeutic outcomes.

SOURCE: Carhart-Harris, R. L., & Nutt, D. J. (2017). Serotonin and brain function: a tale of two receptors. Journal of psychopharmacology (Oxford, England), 31(9), 1091–1120. https://doi.org/10.1177/0269881117725915. (PDF: https://pmc.ncbi.nlm.nih.gov/articles....

#neuralplasticity #neuroscience #serotonin #neurobiology #5ht1a #5ht2a #serotonin2a #serotonin1a #stability #plasticity #neuroplasticity #neurogenesis #bdnf #mtor #activecoping #passivecoping #copingstrategies #psychology #psychedelicresearch #psychedelicscience #psychedelictherapy #impulsive #aggression #anxiety #stress #parenting #depression #learning #cognition #ssri #mentalhealthresearch #entropy #entropicbrain #resilience #adversity #positivemood #distresstolerance #setandsetting @BrennaBrayPhD @NIHVideoCast @NIMHgov @NIH_NCCIH @TheAPAVideo @AmericanPsychiatricAssociation @BBRFoundation @naropauniversity @naropaallianceforpsychedel7015 @nunmedu @PsychedelicsToday @yalepsychedelicsciencegrou9534 @stanfordpsychedelicscience12 @harvarddepartmentofpsychol2330 @OxfordPsychedelicSociety @uclapsychedelic7411 @UCBCSP @ucsbpsychedelicclub9920 @mghcenterfortheneuroscienc28 @UCBCSP @mapsmdma @psychedelicsocietyofminnes8055 @Neuroscience @BosqueNeuroscience @BosqueNeuroscience @prsneurosciences @neuroscienceonline2420 @uofubraininstitute @Carhartharrislab @Plasticity @JoshNeuroplasticitySchool @Motivate_Neuroplasticity @neuroplasticcare8249 @neurogenesisinstitute2659 @neurogenesisinstitute9900 @5-ht2a ​