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Robert C. Malenka

11 papers in the library · 307 citations · publishing 2016-2025

Papers

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CNSC-36. PSILOCYBIN INDUCES SUSTAINED GLIOMA GROWTH THROUGH SEROTONERGIC AND TRKB PATHWAYS

Neuro-Oncology November 1, 2025 Richard Drexler, Belgin Yalçın, Rebecca Mancusi et al.

Abstract High-grade gliomas are the most aggressive form of brain tumors, and neuronal activity has emerged as a driver of glioma pathophysiology. Activity-dependent glioma growth results from paracrine factor signaling and bona fide neuron-to-glioma synapses that integrate glioma cells into brain-wide neuronal circuits. Here, we report how glioma cells integrate into serotonergic (5-HT)...

Psilocybin has no immediate or persistent analgesic effect in acute and chronic mouse pain models

bioRxiv (Cold Spring Harbor Laboratory) July 7, 2025 Akila Ram, Austen B Casey, Robert C. Malenka et al. 2 citations preprint

Abstract The psychedelic psilocybin may have lasting therapeutic effects for patients with chronic pain syndromes. Some clinical and preclinical data suggest these putative benefits derive from direct analgesic effects. However, this possibility has not been comprehensively tested in preclinical models. Here, we show that psilocybin is not analgesic over a range of doses across multiple pain...

Ketamine evokes acute behavioral effects via μ-opioid receptor expressing neurons of the central amygdala.

Biological Psychiatry May 5, 2025 Matthew B Pomrenze, Sam Vaillancourt, Pierre Llorach et al. 11 citations

Ketamine has anesthetic, analgesic, and antidepressant properties which may involve multiple neuromodulatory systems. In humans, the opioid receptor (OR) antagonist naltrexone blocks the antidepressant effect of ketamine. This mechanism may differentiate ketamine from other NMDA receptor antagonists. Animal models that reflect OR-dependent behavioral effects of ketamine may shed light on the...

A multi-institutional investigation of psilocybin’s effects on mouse behavior

bioRxiv (Cold Spring Harbor Laboratory) April 9, 2025 Odilia D Lu, Katrina White, Kendall Raymond et al. 18 citations preprint

ABSTRACT Studies reporting novel therapeutic effects of psychedelic drugs are rapidly emerging. However, the reproducibility and reliability of these findings could remain uncertain for years. Here, we implemented a multi-institutional collaborative approach to define the robust and replicable effects of the psychedelic drug psilocybin on mouse behavior. Five laboratories performed the same...

5-HT2C receptors in the nucleus accumbens constrain the rewarding effects of MDMA.

bioRxiv : the preprint server for biology October 22, 2024 Matthew B Pomrenze, Sam Vaillancourt, Juliana S Salgado et al. 1 citation preprint

MDMA is a promising adjunct to psychotherapy and has well-known abuse liability, although less than other amphetamine analogs. While the reinforcing dopamine (DA)-releasing properties of MDMA are on par with methamphetamine (METH), MDMA is a far more potent serotonin (5-HT) releaser, via the 5-HT transporter (SERT). MDMA-mediated 5-HT release in a major reward center, the nucleus accumbens...

MDMA enhances empathy-like behaviors in mice via 5-HT release in the nucleus accumbens.

Science Advances April 26, 2024 Ben Rein, Kendall Raymond, Cali Boustani et al. 37 citations

MDMA (3,4-methylenedioxymethamphetamine) is a psychoactive drug with powerful prosocial effects. While MDMA is sometimes termed an "empathogen," empirical studies have struggled to clearly demonstrate these effects or pinpoint underlying mechanisms. Here, we paired the social transfer of pain and analgesia-behavioral tests modeling empathy in mice-with region-specific neuropharmacology,...

Opioid receptor expressing neurons of the central amygdala gate behavioral effects of ketamine in mice.

bioRxiv : the preprint server for biology March 6, 2024 Matthew B Pomrenze, Sam Vaillancourt, Pierre Llorach et al. 1 citation preprint

Ketamine has anesthetic, analgesic, and antidepressant properties which may involve multiple neuromodulatory systems. In humans, the opioid receptor (OR) antagonist naltrexone blocks the antidepressant effect of ketamine. It is unclear whether naltrexone blocks a direct effect of ketamine at ORs, or whether normal functioning of the OR system is required to realize the full antidepressant...

UNRAVELing the synergistic effects of psilocybin and environment on brain-wide immediate early gene expression in mice.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology November 1, 2023 Daniel Ryskamp Rijsketic, Austen B Casey, Daniel A. N. Barbosa et al. 49 citations

The effects of context on the subjective experience of serotonergic psychedelics have not been fully examined in human neuroimaging studies, partly due to limitations of the imaging environment. Here, we administered saline or psilocybin to mice in their home cage or an enriched environment, immunofluorescently-labeled brain-wide c-Fos, and imaged iDISCO+ cleared tissue with light sheet...

Distinct neural mechanisms for the prosocial and rewarding properties of MDMA

Science Translational Medicine December 11, 2019 Boris D. Heifets, Juliana S Salgado, Madison Taylor et al. 119 citations

-fenfluramine, a selective serotonin-releasing compound. By dissociating the mechanisms of MDMA's prosocial effects from its addictive properties, we provide evidence for a conserved neuronal pathway, which can be leveraged to develop novel therapeutics with limited abuse liability.