Neuroscience
July 1, 1993
E O'Hearn, M E Molliver
220 citations
The psychoactive compounds ibogaine and harmaline, both beta-carboline derivatives known to cause hallucinations and tremor, can damage specific neurons in the cerebellum. In rats, a single treatment with either drug led to the degeneration of Purkinje cells in narrow, striped regions of the cerebellar vermis, as shown by loss of specific neuronal proteins and silver staining of dying cells. The damage was confined to parasagittal stripes, matching the organization of climbing fiber inputs from the inferior olive. The authors conclude that both drugs have selective neurotoxic effects on Purkinje cells and suggest that sustained activation of inferior olivary neurons may cause excitotoxic degeneration via release of an excitatory amino acid from climbing fiber terminals.
Neuroreport
August 21, 1995
E O'Hearn, P Zhang, M E Molliver
77 citations
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.
Neuroreport
March 1, 1993
E O'Hearn, D B Long, M E Molliver
72 citations
Ibogaine, a drug proposed for treating addiction, activates glial cells in the cerebellum of rats, indicating possible neurotoxicity. After one to three doses of ibogaine (100 mg per kg of body weight), markers for microglia and astrocytes increased, and these cells changed shape. The activated glial cells appeared in striped patterns within the cerebellar vermis, suggesting degeneration of Purkinje neurons.
Neuroscience
January 1, 2004
E O'Hearn, M E Molliver
16 citations
Ibogaine, a tremorigenic hallucinogen proposed for treating addiction, causes degeneration of Purkinje cells in the cerebellum, primarily in the vermis. Previous work suggested ibogaine itself is not directly toxic; instead, it excites inferior olivary neurons, leading to excessive glutamate release and excitotoxic injury. Testing whether the non-NMDA receptor antagonist GYKI-52466 could protect against this injury, rats received ibogaine plus GYKI-52466. The antagonist did not protect at the doses used; instead, co-administration increased toxicity, causing more extensive Purkinje cell degeneration. The reasons are unclear, but the findings indicate that glutamate antagonists can worsen excitotoxic injury under some conditions, urging caution in clinical use and highlighting the complexity of glutamate receptor contributions to neuronal damage.