An examination of the consequences of chronic exposure to Mitragyna speciosa during adolescence on learning and memory in adulthood

Abstract

Although an emerging drug of concern in the United States and Europe, the active alkaloids associated the Mitragyna speciosa plant have long been utilized for a number of purposes ranging from use as an antitussive to that of anti-inflammatory or analgesic purposes. Known by a number of common names, in the United States it is normally legally sold as Kratom. However, little is known about the consequences of the main constituent, mitragynine or any of the more than two dozen identified plant alkaloids on neuropsychological development, learning and memory, and behavior. In the present experiment, adolescent rats were given repeated injections of saline, 15 mg/kg, or 50 mg/kg of Mitragyna speciosa extract. Once the animals reached 107 days of age, they were assessed for general activity, retention on a step-down passive avoidance task, trained using tasks with spatial components of various levels of difficulty, a spatial learning set task, and a plus maze response learning task. In some but not all of the Morris water maze tasks, escape latencies for the 50 mg/kg but not 15 mg/kg rats were significantly longer than that of saline control animals. Nonetheless, performance across groups on probe trials was comparable. In addition, during learning set testing the escape times for the three groups were comparable and, more important, they were able to respond on trial two on the basis of what they learned on the first trial by the end of training. For plus maze response learning testing, all three groups made a comparable number of reference memory errors. Conversely, the 50 mg/kg drug group made significantly more total and working memory errors than the saline-treated animals. The results suggest that chronic exposure to the alkaloids present in legally available Kratom during adolescence is capable of producing a variety of subtle but lasting changes affecting spatial and working memory performance in adulthood, well after the exposure to Kratom has ended.