Ibogaine Administration Modifies GDNF and BDNF Expression in Brain Regions Involved in Mesocorticolimbic and Nigral Dopaminergic Circuits

Summary & key facts

In this rat study, animals got a single injection of ibogaine at 20 mg/kg or 40 mg/kg and the researchers measured three neurotrophic factors (GDNF, BDNF, NGF) in four brain regions (VTA, prefrontal cortex, nucleus accumbens, substantia nigra) at 3 and 24 hours. The main changes appeared at 24 hours: GDNF mRNA and GDNF protein rose in the VTA only after 40 mg/kg, BDNF mRNA rose strongly in several regions after both doses (but in the VTA only after 40 mg/kg) while BDNF protein did not increase, proBDNF protein rose in the nucleus accumbens after both doses, and NGF mRNA increased broadly after 40 mg/kg. The authors say these 24‑hour changes occur after the drug is cleared and that more resea

Key facts:

• Rats were given a single intraperitoneal dose of ibogaine at either 20 mg/kg (I20) or 40 mg/kg (I40).
• Measurements were made at two times: 3 hours and 24 hours after injection; the main increases in neurotrophic factor expression were seen at 24 hours.
• GDNF mRNA was selectively upregulated in the Ventral Tegmental Area (VTA) and Substantia Nigra (SN) only in the 40 mg/kg (I40) group at 24 hours.
• GDNF protein increased in the VTA only after the 40 mg/kg dose; no GDNF protein increase was reported for the 20 mg/kg dose.
• Both 20 mg/kg and 40 mg/kg doses caused large increases in BDNF mRNA in the Nucleus Accumbens (NAcc), Substantia Nigra (SN), and Prefrontal Cortex (PFC); in the VTA a significant BDNF mRNA increase was seen only after 40 mg/kg.
• No significant increase in mature BDNF protein was found in the studied brain areas at the tested times.
• An increase in the precursor proBDNF protein was detected in the Nucleus Accumbens after both 20 mg/kg and 40 mg/kg doses.
• NGF (Nerve Growth Factor) mRNA was upregulated in all four regions after 40 mg/kg; the 20 mg/kg dose increased NGF mRNA only in the PFC and VTA.
• The authors note that 24 hours is a time when ibogaine is no longer present in rat brain tissue, so the observed changes may reflect longer‑lasting effects, and they emphasize that further research is needed to understand how these changes

Abstract

Ibogaine is an atypical psychedelic alkaloid, which has been subject of research due to its reported ability to attenuate drug-seeking behavior. Recent work ...

Topics

Nerve injury and regeneration Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies

Categories

Cellular and Molecular Neuroscience Life Sciences Neuroscience

Tags

Biochemistry Biology Brain-derived neurotrophic factor Chemistry Dopamine Dopaminergic Downregulation and upregulation GDNF family of ligands Gene Glial cell line-derived neurotrophic factor Internal medicine Medicine Neuroscience Neurotrophic factors Nucleus accumbens Pharmacology Receptor Substantia nigra Ventral tegmental area