Ibogalogs improve spatial and recognition memory in rodents through a mechanism involving 5-HT2A receptor activation-enhanced NMDA receptor activity in hippocampal pyramidal CA1 neurons
Abdeslam Chagraoui, Luis A Haro Santillan, Renata Bocian, Sarah J. Cohen, Yusely Ruiz, Mark Knox, Paulina Kaźmierska, Weronika Zimoń, Robert W. Stackman, Jorge Flores‐hernández, Hugo R Arias
Biomedicine & Pharmacotherapy November 13, 2025 DOI: 10.1016/j.biopha.2025.118742 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rodents (mice) |
| Interventions | IBG TBG) |
| Measures | Barnes maze, novel object recognition task (NORT) |
| Topics | Serotonin |
| Keywords | Hippocampal formation Nmda receptor Hippocampus Glutamate receptor Electrophysiology Recognition memory In vivo Long-term depression Long-term potentiation Spatial memory Ampa receptor Neurotransmission Memoria |
| Citations | 5 |
| Key findings | Ibogalogs enhance short- and long-term memory in rodents via 5-HT2A/2CR activation, modulating NMDAR activity and theta rhythm in hippocampal CA1 neurons. |
Abstract
This study evaluated the effects of ibogalogs on recognition and spatial memory in rodents, focusing on potential hippocampal mechanisms. The Barnes maze study demonstrated that ibogaminalog (DM506) and ibogainalog (IBG) improved short- (30 min) and long-term (24 and 72 h) spatial memory in mice, whereas tabernanthalog (TBG) showed less efficacy. The novel object recognition task (NORT) results showed that DM506, but not TBG or IBG, enhanced long-term (24 h) recognition memory. Serotonin type 2 A and 2 C receptors (5-HT2A/2C Rs) involvement, in these effects was demonstrated by their partial inhibition using the selective antagonists volinanserin and SB242084, respectively. Furthermore, in vitro and in vivo electrophysiological studies have demonstrated a mechanistic link between ibogalogs and hippocampal function. TBG (1-5 µM) and DM506 (0.6 µM) significantly increased theta rhythm power and amplitude in CA1. In contrast, volinanserin (alone) and higher concentrations of DM506 (0.8-1 µM) significantly decreased these parameters. In acutely dissociated CA1 pyramidal neurons, DM506 enhanced the N-methyl-D-aspartate receptor (NMDAR)-mediated current peak amplitude (EC50 = 20 ± 15 nM), which was blocked by Mg2 + , indicating NMDAR involvement. Interestingly, TBG had a lower effect than that of DM506 at high concentrations. Importantly, selective 5-HT2A/2CR antagonists inhibited the promnesic effects of ibogalogs, NMDAR enhancement, and theta power increase, indicating the importance of these receptor subtypes. These findings suggest that ibogalogs enhance short- and long-term memory in rodents via 5-HT2A/2CR activation, with a clearer role for 5-HT2ARs in modulating NMDAR activity and theta rhythm in hippocampal CA1 neurons, key processes in memory and attention.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 2
- Psychoplastogens to Reduce Persistent Cognitive Symptoms for Traumatic Brain Injury as a Chronic Condition Journal of Neurotrauma October 19, 2026
- Beyond the Genomic Storm: Evaluating Tabernanthalog as a Potential Scaffold for Silent Neuroplasticity and Broad-Spectrum Therapy International Journal of Molecular Sciences March 20, 2026
Cites 8
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- A non-hallucinogenic psychedelic analogue with therapeutic potential. Nature 2021
- A non-hallucinogenic LSD analog with therapeutic potential for mood disorders. Cell Reports March 28, 2023
- An analog of psychedelics restores functional neural circuits disrupted by unpredictable stress Molecular Psychiatry May 25, 2021
- Non-hallucinogenic compounds derived from iboga alkaloids alleviate neuropathic and visceral pain in mice through a mechanism involving 5-HT2A receptor activation. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie June 17, 2024
and 3 more in the library