Abstract

Intro
Tolerance is a compensatory biological mechanism for repeated drug exposure which can also occur between different drugs as cross-tolerance. The present study investigates the behavioural effects of psilocybin tolerance in operant lever pressing and pharmacological effects with quipazine cross-tolerance in head twitch response.

Methods
Adult male Wistar rats were trained for lever pressing with a reward of sweet water for one week. After the shaping phase, psilocybin group received 1 mg/kg and 4 mg/kg (i.p.) psilocybin while control group was receiving saline for 5 consecutive days of operant lever pressing. On the 6th day, both groups were given 2 mg/kg quipazine to assess the psilocybin cross-tolerance on quipazine-induced head twitch response.

Results
Psilocybin tolerance resulted in the disruption of hallucinogenic pause in operant lever-pressing on the 2nd day with significantly higher presses in psilocybin group compared to the number of presses on the 1st day. Saline group did not show significant change in the number of presses between the days. This result shows the quick emergence of behavioural tolerance to psilocybin. On the 6th day of quipazine challenge, saline group showed significantly higher number of head twitches compared to psilocybin group. This result indicates the cross-tolerance of psilocybin to quipazine-induced head twitch response.

Conclusion
Overall, repeated psilocybin administration was coupled with repetitive operant conditioning sessions caused an acute behavioural tolerance with the disruption of hallucinogenic pause as well as a pharmacological cross-tolerance to quipazine with a possible .