Autoregulation of glial cell line-derived neurotrophic factor expression: implications for the long-lasting actions of the anti-addiction drug, Ibogaine.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology November 1, 2006 Dao‐yao He, Dorit Ron, Dao‐yao He et al. 67 citations
A single dose of Ibogaine, a putative anti-addiction drug, triggers a sustained increase in glial cell line-derived neurotrophic factor (GDNF) in midbrain cells. Using cultured dopaminergic-like SHSY5Y cells, short-term Ibogaine exposure initiated a self-sustaining positive feedback loop: GDNF mRNA rose, protein was expressed, and the GDNF signaling pathway activated, which further increased GDNF mRNA. This autoregulatory cycle explains Ibogaine's long-lasting reduction of drug craving in humans and alcohol and drug intake in rodents. The discovery of this GDNF-mediated feedback loop suggests potential for GDNF-based treatments for addiction and neurodegenerative diseases.