title: Chronic mitragynine (kratom) enhances punishment resistance in natural reward seeking and impairs place learning in mice.
abstract: Kratom (Mitragyna speciosa) is a widely abused herbal drug preparation in Southeast Asia. It is often consumed as a substitute for heroin, but imposing itself unknown harms and addictive burdens. Mitragynine is the major psychostimulant constituent of kratom that has recently been reported to induce morphine-like behavioural and cognitive effects in rodents. The effects of chronic consumption on non-drug related behaviours are still unclear. In the present study, we investigated the effects of chronic mitragynine treatment on spontaneous activity, reward-related behaviour and cognition in mice in an IntelliCage® system, and compared them with those of morphine and Δ-9-tetrahydrocannabinol (THC). We found that chronic mitragynine treatment significantly potentiated horizontal exploratory activity. It enhanced spontaneous sucrose preference and also its persistence when the preference had aversive consequences. Furthermore, mitragynine impaired place learning and its reversal. Thereby, mitragynine effects closely resembled that of morphine and THC sensitisation. These findings suggest that chronic mitragynine exposure enhances spontaneous locomotor activity and the preference for natural rewards, but impairs learning and memory. These findings confirm pleiotropic effects of mitragynine (kratom) on human lifestyle, but may also support the recognition of the drug's harm potential.
authors.affiliation: Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Malaysia.|Centre for Neuroscience Services and Research, Universiti Sains Malaysia, Malaysia.
authors.forename: Nurul Iman W
authors.initials: NIW
authors.lastname: Ismail
authors.affiliation: Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Malaysia.|Centre for Neuroscience Services and Research, Universiti Sains Malaysia, Malaysia.
authors.forename: Nanthini
authors.initials: N
authors.lastname: Jayabalan
authors.affiliation: Centre for Drug Research, Universiti Sains Malaysia, Malaysia.
authors.forename: Sharif Mahsufi
authors.initials: SM
authors.lastname: Mansor
authors.affiliation: Section of Addiction Medicine, Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University Erlangen-Nuremberg, Germany.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Müller
authors.affiliation: Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Malaysia.|Centre for Neuroscience Services and Research, Universiti Sains Malaysia, Malaysia.
authors.forename: Mustapha
authors.initials: M
authors.lastname: Muzaimi
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D007858:Learning / Q000187:drug effects*; D008297:Male; D051379:Mice; D011678:Punishment; D012201:Reward; D046948:Secologanin Tryptamine Alkaloids / Q000494:pharmacology*; D019966:Substance-Related Disorders / Q000150:complications*
chemical_list: D046948:Secologanin Tryptamine Alkaloids; C001801:mitragynine
keywords: kratom; mitragynine; morphine; place learning; sucrose preference; Δ-9-tetrahydrocannabinol (Δ9-THC)