Rewarding Effects of the Psychedelics Ayahuasca and Psilocybin in the Conditioned Place Preference Paradigm
Digital Library of Theses and Dissertations (Universidade de São Paulo) May 12, 2025 Vítor Bruno
In male C57Bl/6 mice, ayahuasca at 15 mg DMT/kg produced a conditioned place preference, indicating reinforcing potential. Ayahuasca did not prevent the acquisition of cocaine-induced CPP, but acute administration of ayahuasca (12.5 or 15 mg DMT/kg) blocked the expression of cocaine CPP, and both doses prevented reinstatement of cocaine CPP. Gene expression analysis in the prefrontal cortex showed upregulation of Arc, Cebpd, Egr1, Egr2, Egr4, Fos, Junb, and Nr4a1, and downregulation of Reln. In male Sprague-Dawley rats, psilocybin (10 mg/kg) did not produce CPP under either alternate-day or consecutive-day conditioning. Consecutive-day psilocybin reduced neuronal activity in the ventral tegmental area after 48 hours of withdrawal, without observable behavioral changes.