Date of Award
Master of Science
Deranda Brewer Lester
James G. Murphy
Nicholas W. Simon
Kratom, derived from the plant Mitragyna speciosa, is reported to produce stimulant-like effects at low doses and opiate-like effects at high doses. Mitragynine (MG) and 7-hydroxymitragynine (7-HMG) are the major psychoactive constituents of kratom, but the neural mechanisms of these alkaloids are not clear. Given that the effects of kratom are often compared to those of drugs with a high abuse liability, the current study aimed to determine the effect of MG and 7-HMG on reward-related neurotransmission. In vivo fixed potential amperometry was used to quantify stimulation-evoked phasic dopamine release in the nucleus accumbens (NAc) of anesthetized male and female mice. During dopamine recordings, mice received an i.p. injection of either MG (1,15, or 30 mg/kg i.p.), 7-HMG (0.5, 1, or 2 mg/kg i.p.), or vehicle, and dopamine recordings continued for 90 min. Using specific stimulation parameters, dopamine autoreceptor functioning was measured 30 min post injection. Sex effects were observed following MG but not 7-HMG. In males, there was a significant time x MG dose interaction with the low dose seeming to increase dopamine release relative to vehicle and the higher doses towards the end of the recording period. However, follow-up tests revealed no significant dopamine release differences between doses at specific time points. Low dose MG also increased dopamine autoreceptor functioning (+50% from vehicle) in males. Regarding 7-HMG, both sexes responded similarly with a significant time x 7-HMG dose interaction effect on dopamine release. Follow-up tests revealed significant differences between 7-HMG doses from 60-90 min post injection, with the low dose increasing dopamine release (+18% from vehicle) compared to the high dose (-22% from vehicle). 7-HMG did not alter dopamine autoreceptor functioning. Neither MG nor 7-HMG altered the clearance rate of stimulation-evoked dopamine, indicating no drug effect on dopamine transporter functioning. In conclusion, dose effects were observed following both MG and 7-HMG. The low dose of MG (1 mg/kg) affected dopamine release in males more than females, potentially through actions on dopamine autoreceptors, and in both sexes the low dose of 7-HMG (0.5 mg/kg) increased dopamine release while the high dose (2 mg/kg) had the opposite effect. Although these increases in dopamine release are considerably less than those normally observed in stimulants with a high abuse liability, these findings do suggest that MG and 7-HMG alter dopamine transmission. An increased understanding of the neural mechanisms of kratom may provide insight on its potential uses and abuse liability.
dissertation or thesis originally submitted to the local University of Memphis Electronic Theses & dissertation (ETD) Repository.
Manus, James Paul, "Examining the Effects of Kratom Alkaloids on Mesolimbic Dopamine Release" (2021). Electronic Theses and Dissertations. 2207.