Pharmacological Mechanisms Involved in Sensory Gating Disruption Induced by (±)-3,4-Methylene- Dioxymethamphetamine (MDMA): Relevance to Schizophrenia

Lee, Jaime; Thwaites, Shane J.; Gogos, Andrea; Buuse, Maarten van den

doi:10.3390/brainsci10010044

Cited by 6 publications

(3 citation statements)

References 51 publications

(76 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This gating could serve to reduce sensory input during 'internal 'hippocampal memory processing, effectively decreasing potential interference that would disrupt memory consolidation (44,45). While the mechanism of 5-HT's effect on long-range neural synchrony is not yet clear, it has been shown that 5-HT can alter sensory gating dependent on communication between the thalamus and hippocampus (46). Furthermore, a recent study showed that type 2 dentate spikes (DS2s) in the hippocampus constitute substates of high arousal within immobility periods (47).…”

Section: Discussionmentioning

confidence: 99%

Ultraslow serotonin oscillations in the hippocampus delineate substates across NREM and waking

Cooper,

Parthier,

Sibille

et al. 2024

Preprint

View full text Add to dashboard Cite

Beyond the vast array of functional roles attributed to serotonin (5-HT) in the brain, changes in 5-HT levels have been shown to accompany changes in behavioral states, including WAKE, NREM and REM sleep. Whether 5-HT dynamics at shorter time scales can be seen to delineate substates within these larger brain states remains an open question. Here, we performed simultaneous recordings of extracellular 5-HT using a recently-developed G Protein–Coupled Receptor-Activation–Based 5-HT sensor (GRAB5-HT3.0) and local field potential (LFP) in the hippocampal CA1, which revealed the presence of prominent ultraslow (<0.05 Hz) 5-HT oscillations both during NREM and WAKE states. Interestingly, the phase of these ultraslow 5-HT oscillations was found to distinguish substates both within and across larger behavioral states. Hippocampal ripples occurred preferentially on the falling phase of ultraslow 5-HT oscillations during both NREM and WAKE, with higher power ripples concentrating near the peak specifically during NREM. By contrast, hippocampal-cortical coherence was strongest and microarousals and EMG peaks were most prevalent during the rising phase in both wake and NREM. Overall, ultraslow 5-HT oscillations delineate substates within the larger behavioral states of NREM and WAKE, thus potentially temporally segregating internal memory consolidation processes from arousal-related functions.

show abstract

Section: Discussionmentioning

confidence: 99%

Ultraslow serotonin oscillations in the hippocampus delineate substates across NREM and waking

Cooper,

Parthier,

Sibille

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Importantly, MDMA can affect the perception of sound. Animal models show that auditory sensory gating is directly affected during MDMA use ( 45 ), and that this action depends on the serotonin receptor 5-HT2A ( 46 ). Since auditory gating may also be affected in misophonia ( 24 ), it would be of interest to see if MDMA administration could counteract these auditory gating abnormalities, but this remains to be examined.…”

Section: Proposed Mdma Effects On Relevant Misophonia Symptomsmentioning

confidence: 99%

MDMA for the treatment of misophonia, a proposal

Webb¹,

Keane²

2022

Front. Psychiatry

View full text Add to dashboard Cite

Misophonia is a disorder characterized by negative physical and emotional reactions to certain trigger sounds, such as chewing food. Up to 50% of population samples endorse some symptoms of misophonia, with about 20% having symptoms that impair normal life functioning. Most misophonia patients exhibit intense negative emotions and autonomic arousal (the fight-flight-freeze response) in response to a trigger, similarly to how someone with post-traumatic stress disorder (PTSD) might respond to a trauma trigger. Curiously, misophonia trigger sounds are often most distressing when coming from a specific person, suggesting the disorder may be responsive to interpersonal relationship factors. Treatment of misophonia is currently limited to the use of hearing modifications (e.g., earplugs or headphones) and psychotherapy, but many patients continue to suffer despite these best efforts. Phase 3 clinical trials suggest that MDMA is efficacious at treating the symptoms of autonomic arousal, negative emotions, and interpersonal suffering found in PTSD. As such, we propose that MDMA may represent an ideal treatment for some suffering from severe misophonia. In this perspective article, we review the symptoms of misophonia, and outline how MDMA may be uniquely suited for treating it, perhaps using a protocol analogous to the MAPS Phase 3 studies for PTSD.

show abstract

“…MDMA use has been previously shown to induce psychosis in single case studies (20)(21)(22). In rats MDMA has been shown to disrupt mechanisms of auditory sensory gating via its involvement in both dopaminergic and serotonergic pathways (23,24). Sensory gating is a form of information processing where irrelevant stimuli are being ignored and is being hypothesized to be deficient in patients suffering from PDs (25).…”

Section: Introductionmentioning

confidence: 99%

Attenuated Psychotic Symptoms in Adolescents With Chronic Cannabis and MDMA Use

et al. 2022

View full text Add to dashboard Cite

ObjectivesBoth substance use, on the one hand, and the first signs of psychosis, on the other, commonly begin in adolescence. Adolescents with substance use disorder (SUD) frequently show recreational use of cannabis and 3,4-methylenedioxymethamphetamine (MDMA). When attenuated psychotic symptoms (APS) occur during the course of SUD, they are commonly attributed to the cannabis use, neglecting the role of other substances abused, such as MDMA in the risk of psychosis.MethodsWe analyzed retrospective self-reports on APS (Prodromal Questionnaire, PQ-16) and amount of cannabis and MDMA use in n = 46 adolescent psychiatry outpatients with SUD. N = 17 (35%) individuals reported MDMA consume additional to cannabis. Furthermore, we examined the associations of APS with cannabis and MDMA use in stepwise hierarchical regressions while controlling for trauma history, birth complications and gender.ResultsAPS were not related to cannabis (B = 0.04, p = 0.842), but to MDMA use (B = 4.88, p = 0.001) and trauma history (B = 0.72, p = 0.001). Gender (B = −0.22, p = 0.767) and birth complications (B = −0.68, p = 0.178) were not associated with APS.DiscussionOur results indicate that MDMA use additional to cannabis use is associated with APS among adolescent SUD patients. Contrary to our expectations, we did not see an association of cannabis use and APS. We speculate that cannabis increases the risk for psychosis after a longer period of use and in combination with other risk factors, such as trauma history. Clinicians should screen for APS among SUD patients using MDMA and cannabis in order to adapt treatment plans of SUDs. Future research should validate these findings in longitudinal studies including polysubstance use and trauma history.

show abstract

Pharmacological Mechanisms Involved in Sensory Gating Disruption Induced by (±)-3,4-Methylene- Dioxymethamphetamine (MDMA): Relevance to Schizophrenia

Cited by 6 publications

References 51 publications

Ultraslow serotonin oscillations in the hippocampus delineate substates across NREM and waking

Ultraslow serotonin oscillations in the hippocampus delineate substates across NREM and waking

MDMA for the treatment of misophonia, a proposal

Attenuated Psychotic Symptoms in Adolescents With Chronic Cannabis and MDMA Use

Contact Info

Product

Resources

About