Psilocybin prevents activity-based anorexia in female rats by enhancing cognitive flexibility: contributions from 5-HT1A and 5-HT2A receptor mechanisms DOI Creative Commons
Kyna‐Anne Conn,

LK Milton,

Kaixin Huang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 13, 2023

Abstract Psilocybin has shown promise for alleviating symptoms of depression and is currently in clinical trials the treatment anorexia nervosa (AN), a condition that characterised by persistent cognitive inflexibility. Considering enhanced flexibility after psilocybin reported to occur individuals with depression, it plausible could improve AN breaking down A mechanistic understanding actions required tailor application most likely respond positive outcomes. This can only be achieved using incisive neurobiological approaches animal models. Here, we use activity-based (ABA) rat model comprehensively assess aspects reinforcement learning show (post-acutely) improves body weight maintenance female rats facilitates flexibility, specifically via improved adaptation initial reversal reward contingencies. Further, reveal involvement signalling through serotonin (5-HT) 1A 5-HT2A receptor subtypes specific learning, demonstrating 5-HT1A antagonism negates enhancing effects psilocybin. Moreover, elicits transient increase decrease cortical transcription these receptors ( Htr2a Htr1a , respectively), further reduction abundance transcripts exposed ABA model. Together, findings support hypothesis ameliorate inflexibility context highlight need better understand therapeutic mechanisms independent binding.

Language: Английский

Psilocybin restrains activity-based anorexia in female rats by enhancing cognitive flexibility: contributions from 5-HT1A and 5-HT2A receptor mechanisms DOI Creative Commons
Kyna‐Anne Conn, Laura K Milton, Kaixin Huang

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(10), P. 3291 - 3304

Published: April 27, 2024

Abstract Psilocybin has shown promise for alleviating symptoms of depression and is currently in clinical trials the treatment anorexia nervosa (AN), a condition that characterised by persistent cognitive inflexibility. Considering enhanced flexibility after psilocybin reported to occur individuals with depression, it plausible could improve AN breaking down A mechanistic understanding actions required tailor application most likely respond positive outcomes. This can only be achieved using incisive neurobiological approaches animal models. Here, we use activity-based (ABA) rat model comprehensively assess aspects reinforcement learning show (post-acutely) improves body weight maintenance female rats facilitates flexibility, specifically via improved adaptation initial reversal reward contingencies. Further, reveal involvement signalling through serotonin (5-HT) 1 5-HT2A receptor subtypes specific learning, demonstrating 5-HT1A antagonism negates enhancing effects psilocybin. Moreover, elicits transient increase decrease cortical transcription these receptors ( Htr2a Htr1a , respectively), further reduction abundance transcripts exposed ABA model. Together, findings support hypothesis ameliorate inflexibility context highlight need better understand therapeutic mechanisms independent binding.

Language: Английский

Citations

16
A transdiagnostic and translational framework for delineating the neuronal mechanisms of compulsive exercise in anorexia nervosa DOI Creative Commons
Kyna‐Anne Conn, Kaixin Huang, Sasha Gorrell

et al.

International Journal of Eating Disorders, Journal Year: 2024, Volume and Issue: 57(7), P. 1406 - 1417

Published: Jan. 4, 2024

Abstract Objective The development of novel treatments for anorexia nervosa (AN) requires a detailed understanding the biological underpinnings specific, commonly occurring symptoms, including compulsive exercise. There is considerable bio‐behavioral overlap between AN and obsessive‐compulsive disorder (OCD), therefore it plausible that similar mechanisms underlie behavior in both populations. While association these conditions widely acknowledged, defining shared OCD approach. Methods We present an argument better neurobiological underpin exercise can be achieved two critical ways. First, by applying framework neuronal control to AN, second, taking advantage activity‐based (ABA) rodent model directly test this context feeding pathology. Results A cross‐disciplinary approach spans preclinical, neuroimaging, clinical research as well neurocircuitry advance our when, why, how develops provide targets treatment strategies. Discussion In article, we (i) link expression via transition goal‐directed habitual behavior, (ii) disrupted cortico‐striatal circuitry key substrate conditions, (iii) highlight utility ABA understand relevant AN. Public Significance Individuals with who compulsively are at risk worse health outcomes have poorer responses standard treatments. However, remains inadequately understood. Identifying whether neural underlying also controls hyperactivity will aid eating strategies high‐risk population.

Language: Английский

Citations

4
Taking better advantage of the activity-based anorexia model DOI Creative Commons
Claire J. Foldi

Trends in Molecular Medicine, Journal Year: 2023, Volume and Issue: 30(4), P. 330 - 338

Published: Dec. 15, 2023

The lack of specific treatments for anorexia nervosa (AN) is partly driven by an inadequate understanding the neurobiological drivers condition. activity-based (ABA) model recapitulates key characteristics AN in rats and mice, can be used to understand factors that predispose, maintain, rescue anorectic behaviour. With rapidly evolving suite technologies manipulate record neural activity during development ABA, we are better placed than ever before take advantage this unique biobehavioural order develop refine novel AN. This will require a collective effort bridge research disciplines capitalise on knowledge gains from genetics, neurobiology, metabolism, cognition.

Language: Английский

Citations

5
Psilocybin prevents activity-based anorexia in female rats by enhancing cognitive flexibility: contributions from 5-HT1A and 5-HT2A receptor mechanisms DOI Creative Commons
Kyna‐Anne Conn,

LK Milton,

Kaixin Huang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 13, 2023

Abstract Psilocybin has shown promise for alleviating symptoms of depression and is currently in clinical trials the treatment anorexia nervosa (AN), a condition that characterised by persistent cognitive inflexibility. Considering enhanced flexibility after psilocybin reported to occur individuals with depression, it plausible could improve AN breaking down A mechanistic understanding actions required tailor application most likely respond positive outcomes. This can only be achieved using incisive neurobiological approaches animal models. Here, we use activity-based (ABA) rat model comprehensively assess aspects reinforcement learning show (post-acutely) improves body weight maintenance female rats facilitates flexibility, specifically via improved adaptation initial reversal reward contingencies. Further, reveal involvement signalling through serotonin (5-HT) 1A 5-HT2A receptor subtypes specific learning, demonstrating 5-HT1A antagonism negates enhancing effects psilocybin. Moreover, elicits transient increase decrease cortical transcription these receptors ( Htr2a Htr1a , respectively), further reduction abundance transcripts exposed ABA model. Together, findings support hypothesis ameliorate inflexibility context highlight need better understand therapeutic mechanisms independent binding.

Language: Английский

Citations

4