Insights into Serotonin Receptor Trafficking

Darmon, Michèle; Awabdh, Sana Al; Emerit, M.B.; Masson, Justine

doi:10.1016/bs.pmbts.2015.02.009

Cited by 26 publications

(13 citation statements)

References 106 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The half-life of psilocybin and psilocin (the active metabolite of psilocybin) is roughly 3 hours 57,58 , indicating that over 50 half-lives of the drug had passed before the 1 week time point, ensuring elimination of the drug from each participant. Further, while the 5-HT 2A receptor is known to internalize rapidly with both agonism and antagonism, it is thought to be re-expressed roughly 24-48 hours after internalization (in the absence of chronic engagement) 59 , and thus any transient changes in www.nature.com/scientificreports www.nature.com/scientificreports/ receptor dynamics related to psilocybin administration would be resolved by the 1 week time point. Rather than receptor trafficking or other residual pharmacological effects, the reported findings might better be explained by a neuroplastic period during which the neural processing of affective stimuli is altered.…”

Section: Discussionmentioning

confidence: 99%

“…That finding is somewhat puzzling because amygdala response to negative stimuli is abnormally increased in patients with depression 18,78 , and one would expect an antidepressant response to be accompanied by normalization (e.g., decrease) in amygdala response to negative stimuli 79,80 . A potential explanation for this short-term rebound effect in amygdala response may be that increased amygdala response one day after psilocybin administration reflects a transient alteration of serotonergic signaling, as 5-HT 2A receptors are well-known to readily internalize with both agonism and antagonism 59 , including after administration of classic psychedelics 81 , with re-expression occurring up to 48 hours later 59 . It is important to note, however, that increased amygdala reactivity one day after psilocybin was associated with therapeutic outcomes in this sample, and it may be that a subacute rebound process one day after psilocybin is followed by a subsequent drop in amygdala responsiveness at one week (as in the current sample).…”

Section: Comparison Of Current Findings With Recently Reported Literamentioning

confidence: 99%

See 1 more Smart Citation

Emotions and brain function are altered up to one month after a single high dose of psilocybin

Barrett

Doss

Sepeda

et al. 2020

Sci Rep

229

218

View full text Add to dashboard Cite

Psilocybin is a classic psychedelic compound that may have efficacy for the treatment of mood and substance use disorders. Acute psilocybin effects include reduced negative mood, increased positive mood, and reduced amygdala response to negative affective stimuli. However, no study has investigated the long-term, enduring impact of psilocybin on negative affect and associated brain function. Twelve healthy volunteers (7F/5M) completed an open-label pilot study including assessments 1-day before, 1-week after, and 1-month after receiving a 25 mg/70 kg dose of psilocybin to test the hypothesis that psilocybin administration leads to enduring changes in affect and neural correlates of affect. One-week post-psilocybin, negative affect and amygdala response to facial affect stimuli were reduced, whereas positive affect and dorsal lateral prefrontal and medial orbitofrontal cortex responses to emotionally-conflicting stimuli were increased. One-month post-psilocybin, negative affective and amygdala response to facial affect stimuli returned to baseline levels while positive affect remained elevated, and trait anxiety was reduced. Finally, the number of significant resting-state functional connections across the brain increased from baseline to 1-week and 1-month post-psilocybin. These preliminary findings suggest that psilocybin may increase emotional and brain plasticity, and the reported findings support the hypothesis that negative affect may be a therapeutic target for psilocybin. Studies suggest that psilocybin, a classic psychedelic drug (serotonin 2A or 5-HT 2A receptor partial agonist), may have efficacy for the treatment of depression and anxiety 1-3 , tobacco use disorder 4,5 , and alcohol use disorder 6,7. Reduction of clinical symptoms has been shown to last up to 3 3 , 6 1,2 , and 12 8 months after 1 to 3 psilocybin administrations. Despite these promising advances, the neural and psychological mechanisms underlying the enduring therapeutic effects of psychedelic drugs are not well-understood. Two possibly interactive trans-diagnostic targets that may be affected by psilocybin are negative affect and brain network plasticity. Increased negative affect, reduced positive affect, and hypersensitivity to negatively biased information are hallmarks of mood disorders 9-11. Negative affect is also a core component of the cycle of addiction in which craving and withdrawal symptoms experienced after intoxication lead to preoccupation, anticipation, and re-administration of drugs of abuse 12. The amygdala has been shown in clinical and preclinical models to track the salience of stimuli in the environment 13,14 and is highly responsive to negative emotional stimuli 15-17. Abnormally high amygdala reactivity to negative affective stimuli has been implicated in the pathophysiology of depression 18. Areas within the anterior cingulate cortex (ACC) are understood to monitor cognitive conflict 19-22 , are involved in the appraisal and expression of negative emotion 22 , respond to distress levels associated with pain 23 ...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Comparison Of Current Findings With Recently Reported Literamentioning

confidence: 99%

Emotions and brain function are altered up to one month after a single high dose of psilocybin

Barrett

Doss

Sepeda

et al. 2020

Sci Rep

229

218

View full text Add to dashboard Cite

show abstract

“…The serotonergic system is one of the oldest neurotransmitter systems and seven distinct serotonergic receptors (5-HT 1 – 5HT 7 ), each with several subpopulations of receptors (altogether, at least 14 members in the family are known), mediate both central and peripheral control on numerous physiological functions such as sleep-wake cycle, feeding behavior, thermoregulation, nociception, affective (mood) control and sexual behavior, locomotion and motor control (via interactions with the basal ganglia dopaminergic system), blood coagulation, and cardiovascular homeostasis (Darmon et al, 2015). 5-HT receptors are different in terms of localization and downstream signaling.…”

Section: Chemical Neuroanatomy Of the Monoaminergic Systemsmentioning

confidence: 99%

“…5-HT 4 , 5-HT 6 and 5-HT 7 receptors activate adenylyl cyclase through G αS protein. The majority of 5-HT receptors are postsynaptic, except for 5-HT 1B and 5-HT 1D receptors, which are mostly presynaptic, and 5-HT 1A receptors that are located both on presynaptic and postsynaptic membranes (Seyedabadi et al, 2014 and Darmon et al, 2015). …”

Section: Chemical Neuroanatomy Of the Monoaminergic Systemsmentioning

confidence: 99%

Monoaminergic neuropathology in Alzheimer’s disease

Šimić

Leko

Wray³

et al. 2017

Progress in Neurobiology

230

142

View full text Add to dashboard Cite

None of the proposed mechanisms of Alzheimer’s disease (AD) fully explains the distribution patterns of the neuropathological changes at the cellular and regional levels, and their clinical correlates. One aspect of this problem lies in the complex genetic, epigenetic, and environmental landscape of AD: early-onset AD is often familial with autosomal dominant inheritance, while the vast majority of AD cases are late-onset, with the ε4 variant of the gene encoding apolipoprotein E (APOE) known to confer a 5–20 fold increased risk with partial penetrance. Mechanisms by which genetic variants and environmental factors influence the development of AD pathological changes, especially neurofibrillary degeneration, are not yet known. Here we review current knowledge of the involvement of the monoaminergic systems in AD. The changes in the serotonergic, noradrenergic, dopaminergic, histaminergic, and melatonergic systems in AD are briefly described. We also summarize the possibilities for monoamine-based treatment in AD. Besides neuropathologic AD criteria that include the noradrenergic locus coeruleus (LC), special emphasis is given to the serotonergic dorsal raphe nucleus (DRN). Both of these brainstem nuclei are among the first to be affected by tau protein abnormalities in the course of sporadic AD, causing behavioral and cognitive symptoms of variable severity. The possibility that most of the tangle-bearing neurons of the LC and DRN may release amyloid β as well as soluble monomeric or oligomeric tau protein trans-synaptically by their diffuse projections to the cerebral cortex emphasizes their selective vulnerability and warrants further investigations of the monoaminergic systems in AD.

show abstract

“…This delayed effect would be consistent with the timing of serotonin receptor internalisation, a protective mechanism to avoid excitotoxicity. 35 Using worm motility measurements obtained from our automated image-based assay, dose-response curves were also generated for each incubation time as exemplified in Fig. 2 for the 24 h time point.…”

Section: Biological Activitymentioning

confidence: 99%