Effects of kratom alkaloids on mesolimbic dopamine release

Kratom is derived from the leaves of a plant (Mitragyna speciosa) native to Southeast Asia that has been consumed for its complex stimulant-like effects at low doses, opiate-like effects at high doses, to treat mood related issues like anxiety or depression, or to help ameliorate opioid withdrawal symptoms. However, the neural mechanisms of its major psychoactive alkaloids, mitragynine (MG) and 7-hydroxymitragynine (7-HMG), are still not clear. Given that the effects of kratom are often compared to drugs with abuse liabilities, the current study examined the effects of MG and 7-HMG on reward-related neurotransmission. Fixed potential amperometry was used to quantify stimulation-evoked phasic dopamine release in the nucleus accumbens (NAc) of anesthetized male and female mice before and after MG (1, 15, or 30 mg/kg i.p.), 7-HMG (0.5, 1, or 2 mg/kg i.p.), or vehicle. MG reduced dopamine release over the recording period (90 min) in a dose dependent manner, and the low dose of MG significantly increased dopamine autoreceptor functioning in males. Both sexes responded similarly to 7-HMG with the low dose of 7-HMG increasing dopamine release while the high dose decreased dopamine release. 7-HMG did not alter dopamine autoreceptor functioning for either sex. Neither MG nor 7-HMG altered the clearance rate of stimulation-evoked dopamine. Findings suggest that these kratom alkaloids do alter dopamine functioning, although potentially not in a way consistent with classic drugs of abuse. Further investigation of the neural mechanisms of kratom's alkaloids will provide crucial and urgent insight into their therapeutic uses or potential abuse liability.