Ibogaine induces juvenile-like plasticity and modulates functional and structural regulators of plasticity in the adult mouse visual cortex

Background: Psychedelics have emerged as powerful modulators of neural plasticity, yet whether the atypical psychedelic ibogaine can enhance plasticity remains poorly understood. Here, we investigated 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. Results: Adult mice were treated with ibogaine (40 mg/kg, i.p.) or vehicle, and 24 hours later subjected to 4 days of monocular deprivation (MD). Behavioral visual acuity was quantified using the optomotor response test, and structural plasticity was assessed through dendritic spine density analysis following Golgi staining. Ibogaine alone did not alter visual acuity or dendritic spine density in non-deprived adults. However, when coupled with MD, ibogaine restored youthful levels of plasticity: MD significantly reduced visual acuity in the deprived eye and decreased dendritic spine density in the binocular visual cortex of ibogaine-treated, but not vehicle-treated, adult mice. To examine mechanistic correlates of these findings, we quantified perineuronal nets (PNNs), parvalbumin-positive interneurons (PVs), and inhibitory synaptic puncta labeled with the vesicular GABA transporter (vGAT). We found that ibogaine reduced PNN and PV staining intensity and density, decreased the proportion of PVs enwrapped by PNNs, and lowered vGAT-positive puncta density. Conclusions: These results show that ibogaine re- establishes experience-dependent plasticity in the adult visual cortex and that this effect is accompanied by reductions in structural and inhibitory “brakes” on plasticity. Our findings suggest that ibogaine’s long-lasting therapeutic actions can arise, at least partially, from its ability to re-open windows of heightened cortical adaptability.