Effects of N,N‑Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression

• Published in: ACS chemical neuroscience Vol. 9; no. 7; pp. 1582 - 1590
• Main Authors: Cameron, Lindsay P, Benson, Charlie J, Dunlap, Lee E, Olson, David E
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 18.07.2018
• Subjects: Animals; Anti-Anxiety Agents - pharmacology; Antidepressive Agents - pharmacology; Anxiety Disorders - drug therapy; Conditioning, Psychological - drug effects; Depressive Disorder - drug therapy; Disease Models, Animal; Exploratory Behavior - drug effects; Fear - drug effects; Feeding Behavior - drug effects; Male; Motor Activity - drug effects; N,N-Dimethyltryptamine - pharmacology; Rats, Inbred SHR; psychedelic; ayahuasca; post-traumatic stress disorder; DMT; depression; N,N-dimethyltryptamine
• ISSN: 1948-7193; 1948-7193
• DOI: 10.1021/acschemneuro.8b00134

Depression and anxiety disorders are debilitating diseases resulting in substantial economic costs to society. Traditional antidepressants often take weeks to months to positively affect mood and are ineffective for about 30% of the population. Alternatives, such as ketamine, a dissociative anesthetic capable of producing hallucinations, and the psychoactive tisane ayahuasca, have shown great promise due to their fast-acting nature and effectiveness in treatment-resistant populations. Here, we investigate the effects of N,N-dimethyltryptamine (DMT), the principle hallucinogenic component of ayahuasca, in rodent behavioral assays relevant to anxiety and depression using adult, male, Sprague–Dawley rats. We find that while DMT elicits initial anxiogenic responses in several of these paradigms, its long-lasting effects tend to reduce anxiety by facilitating the extinction of cued fear memory. Furthermore, DMT reduces immobility in the forced swim test, which is a characteristic behavioral response induced by many antidepressants. Our results demonstrate that DMT produces antidepressant and anxiolytic behavioral effects in rodents, warranting further investigation of ayahuasca and classical psychedelics as treatments for depression and post-traumatic stress disorder.