Kratom pharmacology: Clues from planarians exposed to mitragynine

Abstract

Mitragynine (MG), the most prevalent bioactive alkaloid in kratom, displays nanomolar affinity for µ, κ and δ opioid receptors and produces opioid-dependent antinociception and dependence in rats. Here, using a battery of behavioral assays, we investigated MG effects in planarians. Acute MG exposure (< 100 μM) did not affect planarian motility or environmental preference, but reduced motility was detected during abstinence from chronic MG (1, 10 μM). MG (10 μM) produced place conditioning effects that were reduced by naltrexone (10 μΜ). These results suggest that MG produces opioid-sensitive reinforcing effects in planarians and MG pharmacology is conserved across different species.

Keywords: Dependence; Invertebrate; Kratom; Mitragynine; Opioid; Place preference; Planarian.

Fig. 1.. Effects of acute MG exposure on planarian motility and environmental preference.

Planarians were exposed to different concentrations (0, 0.1, 1, 10, 100 μM) of MG and motility rate (crossings/min) (A) and percentage of time spent in the light (B) were determined. N=10 planarians/group. ***p < 0.001 compared to MG-naïve group (0 μM).

Fig. 2.. Abstinence from MG results in reduced planarian motility.

Planarians exposed to MG (0, 0.1, 1, 10 μM) for 60 min were then removed and placed into water where motility counts were quantified for 5 min. Data are presented as motility rate (crossings/min). N=12 planarians/group. ***p < 0.001 or *p < 0.05 compared to MG-naïve group (0 μM).

Fig. 3.. MG produces place conditioning effects that are reduced by NTX.

Planarians were conditioned with MG (0.1, 1, 10 μM). Data are presented as the difference in time spent on the MG-paired side score between post-conditioning and pre-conditioning (post-test minus pre-test times). N=12 planarians/group. *p < 0.05 compared to vehicle control (0 μM). (Box) Planarians were conditioned with a fixed concentration of MG (10 μM) by itself or in combination with the opioid antagonist NTX (10 μM). Data are presented as a difference score (difference in time spent on the MG-paired side score between post-conditioning and pre-conditioning). N=17–22 planarians/group. *p < 0.05 compared to vehicle control (0 μM).