Excitotoxic insult due to ibogaine leads to delayed induction of neuronal NOS in Purkinje cells.

Ibogaine triggers degeneration of Purkinje cells in the brain, likely by activating inferior olive neurons that release glutamate at climbing fiber terminals. After ibogaine administration, some Purkinje cells begin expressing NADPH-diaphorase and neuronal NOS, enzymes not normally present in these cells. This NOS induction is delayed, dose-related, and occurs in neurons next to degenerated Purkinje cells. The findings show that nNOS induction can follow excitotoxic injury, but nitric oxide is unlikely to be involved in the initial damage. The late induction and spatial pattern suggest NO may play a role in neuronal recovery or delayed cell death after excitotoxic injury.

Study at a glance

Abstract

Ibogaine causes degeneration of Purkinje cells (PKCs), presumably via activation of neurons in the inferior olive leading to release of glutamate at climbing fiber terminals. Following ibogaine administration, some Purkinje cells express NADPH-diaphorase and neuronal NOS (nNOS), neither of which is present normally in these cells. The induction of NOS is delayed in onset, dose-related, and detected in neurons adjacent to degenerated PKCs. The results demonstrate that nNOS induction can follow excitotoxic neuronal injury or perturbation. However, NO is unlikely to participate in the initial phase of PKC damage. Both the late induction of nNOS and the spatial relationship between damaged and nNOS-expressing PKCs are consistent with a role for NO in either neuronal recovery or delayed cell death following excitotoxic injury.