ACS chemical neuroscience
June 3, 2020
Paola Rodrı Guez, Jessika Urbanavicius, José Pedro Prieto et al.
44 citations
Ibogaine and its main metabolite noribogaine produce antidepressant-like effects in rats, as measured by the forced swim test. Both compounds induced a dose- and time-dependent reduction in immobility without altering locomotor activity. Noribogaine's effect was short-lived (30 minutes) and correlated with high brain concentrations (estimated >8 μM free drug), while ibogaine's effect was significant at 3 hours, when both ibogaine (~0.5 μM) and noribogaine (~2.5 μM) were present at concentrations that alone could not produce the same outcome. The findings suggest a polypharmacological mechanism underlies the antidepressant-like effects.
ChemRxiv
March 19, 2020
Paola Rodrı́guez, Jessika Urbanavicius, José Pedro Prieto et al.
1 citation
Ibogaine and its main metabolite noribogaine produce antidepressant-like effects in rats in a dose- and time-dependent manner, without altering locomotor activity. Noribogaine's effect is short-lived (30 minutes) and correlates with high brain concentrations (estimated > 8 µM free drug), while ibogaine's effect is significant at 3 hours. At that time, both compounds are present in the brain at concentrations (ibogaine ~0.5 µM, noribogaine ~2.4 µM) that alone cannot produce the same behavioral outcome, suggesting a polypharmacological mechanism underlies their antidepressant-like effects.
Neuropharmacology
August 1, 2022
Mireia Tarrés-Gatius, Ximena López-Hill, Lluis Miquel-Rio et al.
Non-competitive NMDA receptor antagonists like PCP and MK-801 produce schizophrenia-like effects, but the specific receptor subunits and brain regions involved are unclear. Using GluN2C knockout mice, the authors found that deleting the GluN2C subunit reduced stereotyped behaviors such as circling, rearing, and ataxia signs induced by PCP and MK-801, indicating better motor coordination. However, other motor effects and sensorimotor gating deficits (pre-pulse inhibition) remained unchanged. PCP and MK-801 activated c-fos in thalamo-cortical networks but reduced it in the cerebellum, with differences between genotypes matching motor coordination changes. Resting-state fMRI showed enhanced cortico-thalamic-cerebellar connectivity in knockout mice that was less disrupted by MK-801. Thus, GluN2C-containing NMDA receptors in cerebellar circuits mediate some motor incoordination effects but not sensorimotor gating deficits.