THE ATYPICAL PSYCHEDELIC IBOGAINE ENHANCES CORTICAL PLASTICITY AND MODULATES KEY REGULATORS OF PLASTICITY IN THE ADULT MOUSE VISUAL CORTEX

Aims: Psychedelics are increasingly recognized as potent modulators of neural plasticity, yet whether the atypical psychedelic ibogaine can enhance cortical plasticity remains unclear. Here, we examined whether a single administration of ibogaine can reinstate juvenile-like, experience-dependent plasticity in the adult mouse visual cortex, a canonical model for studying neuroplasticity.
Methods: Adult mice received ibogaine (40 mg/kg, i.p.) or vehicle and, 24 hours later, underwent 4 days of monocular deprivation (MD). Visual function was assessed measuring behavioral visual acuity using the optomotor response test, while structural plasticity was evaluated by quantifying dendritic spine density following Golgi staining.
Results: Ibogaine alone did not affect visual acuity or dendritic spine density in non-deprived adult mice. In contrast, when paired with MD, ibogaine reinstated youthful plasticity: MD significantly reduced visual acuity in the deprived eye (~25%) and decreased dendritic spine density (~20%) in the binocular visual cortex of ibogaine-treated - but not vehicle-treated - adult mice. To probe underlying mechanisms, we quantified perineuronal nets (PNNs), parvalbumin-positive interneurons (PVs), and the vesicular GABA transporter (vGAT). Ibogaine treatment reduced PNN and PV density and staining intensity, decreased the proportion of PVs enwrapped by PNNs, and lowered vGAT-positive puncta density.
Conclusions: These findings demonstrate that ibogaine reopens experience-dependent plasticity in the adult visual cortex and that this effect is accompanied by a weakening of structural and inhibitory “brakes” on plasticity. Together, our results suggest that ibogaine long-lasting therapeutic actions may arise, at least in part, from its ability to reinstate windows of heightened cortical adaptability.