5-MeO-DMT, a hallucinogen similar to LSD, reduced movement, exploration, and startle responses in rats. These effects were blocked by a drug that targets serotonin 1A receptors but not by drugs that block serotonin 2A receptors, and only partially by a serotonin 2C blocker. This suggests that serotonin 1A receptors play a key role in the behavioral effects of 5-MeO-DMT, challenging the view that only serotonin 2 receptors are responsible for hallucinogenic effects.
The psychoactive tea ayahuasca contains DMT, 5-MeO-DMT, and MAO inhibitors harmine and harmaline. In rats, 5-MeO-DMT alone decreased movement and exploration. When combined with a low dose of harmaline, 5-MeO-DMT produced an initial decrease in locomotion followed by a later increase. This shift depended on inhibition of MAO-A, not MAO-B. The late hyperactivity was blocked by a 5-HT2A receptor antagonist, indicating that 5-HT2A receptors mediate this effect, while a 5-HT1A antagonist had no effect. Thus, harmaline alters 5-MeO-DMT's behavioral effects through MAO-A inhibition, and 5-HT2A receptors drive the delayed hyperactivity.