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.
The designer drug 4'-F-PCP, a derivative of the dissociative anesthetic phencyclidine (PCP), shows a high potential for abuse. In rodents, a 10 mg/kg dose increased movement and rearing, and produced conditioned place preference, indicating rewarding effects. Intravenous self-administration of 1.0 mg/kg/infusion was robust, with a higher breakpoint under progressive ratio schedules, suggesting strong reinforcing properties. The drug altered dopamine transporter and D1 receptor expression in the nucleus accumbens and increased phosphorylated ERK, CREB, c-Fos, and FosB/ΔFosB, indicating activation of dopamine-related signaling pathways. These findings indicate that 4'-F-PCP has significant abuse liability.