Home > Serotonin and brain function: a tale of two receptors.

Carhart-Harris, RL and Nutt, DJ . (2017) Serotonin and brain function: a tale of two receptors. Sage. Journal of Psychopharmacology, 31 (9)

URL: http://journals.sagepub.com/doi/abs/10.1177/026988...

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.


Item Type:Evidence resource
Publication Type:Review
Drug Type:Alcohol or other drugs in general
Intervention Type:AOD disorder, AOD disorder harm reduction
Date:September 2017
Page Range:pp. 1091-1120
Publisher:Sage
Volume:31
Number:9
EndNote:View
Subjects:A Substance use, abuse, and dependence > Theory of substance use > Biological substance use disorder theory
A Substance use, abuse, and dependence > Effects and consequences
E Concepts in biomedical areas > General life processes (physiology)
G Health and disease > State of health > Physical health
J Health care, prevention and rehabilitation > Risk and protective factors

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