Evidence for intravenous self-administration of mitragynine in fentanyl-dependent rats

Kratom (Mitragyna speciosa Korth) is currently used as an alternative for the self-treatment of pain and management of opioid dependence and withdrawal. Due to the opioid-like effect of the plant’s active alkaloid, mitragynine (MG), the evaluation of its ability to maintain self-administration in animal models of opioid dependence appears to be great significance. Here, the ability of MG to cross-substitute to the reinforcing effects of the synthetic narcotic fentanyl is investigated. Rats with implanted catheters were allowed to self-administer fentanyl (2.0 μg/kg/infusion) on a fixed-ratio 1 (FR-1) of schedule of reinforcement. A significant increase in lever pressing indicated the successful acquisition of fentanyl self-administration. Next, rats were presented with saline or various doses of MG. The cross-substitution of MG at three unit doses (0.3, 1.0 and 3.0 mg/kg/infusion) maintained the lever-pressing responses of the fentanyl self-administration while extinction was evident following the substitution of saline for the fentanyl solution. The differences in the profile of MG cross-substitution tests to the baseline level observed during extinction suggest that MG has fentanyl-like reinforcing effects. However, a more thorough examination of its primary reinforcing effects will need to be determined in naive rats to confirm the potential dependence producing effects of MG. :TJPS-2020-0248.R1