Catharanthine Modulates Mesolimbic Dopamine Transmission and Nicotine Psychomotor Effects via Inhibition of α6-Nicotinic Receptors and Dopamine Transporters.
ACS chemical neuroscience May 1, 2024 Benjamin M Williams, Nathan D Steed, Joel T Woolley et al. 7 citations
Catharanthine and 18-methoxycoronaridine (18-MC), iboga alkaloids, reduce nicotine's effects on dopamine transmission and behavior. In male mice, both compounds inhibited evoked dopamine release in the nucleus accumbens core, with catharanthine's effect depending on α4 and α6 nicotinic receptors. Catharanthine slowed dopamine reuptake ex vivo but increased extracellular dopamine in vivo. Both compounds suppressed firing of striatal cholinergic interneurons and acetylcholine currents in oocytes. In male rats, catharanthine and 18-MC blocked nicotine-enhanced locomotor activity, and catharanthine dose-dependently reduced nicotine self-administration without affecting food reinforcement. Combining catharanthine with nicotine increased head twitch responses, suggesting a potential synergistic hallucinogenic effect.