Noribogaine acute administration in rats promotes wakefulness and suppresses REM sleep

• Published in: Psychopharmacology Vol. 241; no. 7; pp. 1417 - 1426
• Main Authors: Castro-Nin, Juan Pedro, Serantes, Diego, Rodriguez, Paola, Gonzalez, Bruno, Carrera, Ignacio, Torterolo, Pablo, González, Joaquín
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.07.2024; Springer Nature B.V
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Brain research; Drug dosages; Electrodes; Electroencephalography - drug effects; Hallucinogens - administration & dosage; Hallucinogens - pharmacology; Ibogaine - administration & dosage; Ibogaine - analogs & derivatives; Ibogaine - pharmacology; Laboratory animals; Male; Neurosciences; Original Investigation; Pharmacology/Toxicology; Polysomnography; Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; REM sleep; Sleep; Sleep and wakefulness; Sleep, REM - drug effects; Sleep, Slow-Wave - drug effects; Sleep, Slow-Wave - physiology; Software; Wakefulness - drug effects; Wakefulness - physiology; Slow-wave sleep; Ibogaine; Psychedelics; EEG; REM sleep
• ISSN: 0033-3158; 1432-2072; 1432-2072
• DOI: 10.1007/s00213-024-06572-2

Ibogaine is a potent atypical psychedelic that has gained considerable attention due to its antiaddictive and antidepressant properties in preclinical and clinical studies. Previous research from our group showed that ibogaine suppresses sleep and produces an altered wakefulness state, which resembles natural REM sleep. However, after systemic administration, ibogaine is rapidly metabolized to noribogaine, which also shows antiaddictive effects but with a distinct pharmacological profile, making this drug a promising therapeutic candidate. Therefore, we still ignore whether the sleep/wake alterations depend on ibogaine or its principal metabolite noribogaine. To answer this question, we conducted polysomnographic recordings in rats following the administration of pure noribogaine. Our results show that noribogaine promotes wakefulness while reducing slow-wave sleep and blocking REM sleep, similar to our previous results reported for ibogaine administration. Thus, we shed new evidence on the mechanisms by which iboga alkaloids work in the brain.