Effects of 5-HT 2A Receptor Activation on Oxycodone Demand after Short and Long Access Self-Administration in Male and Female Rats
Psychedelic Medicine January 7, 2026 Carter J. Richardson, Alice J. McQueney, Thomas Stevens et al.
In rats that self-administered oxycodone, the psychedelic compound DOI reduced how much they valued the drug, but the effect depended on dose, sex, and how much prior access to oxycodone they had. In rats with short access, DOI lowered demand by decreasing consumption at low prices and making demand more elastic. In rats with long access, low doses of DOI still reduced demand, but high doses increased it. Most of DOI's effects were blocked by a 5-HT2A receptor antagonist, but this antagonist alone also reduced demand in long-access rats. A 5-HT2C receptor antagonist did not block DOI's effects and sometimes added to them.