Mitochondrial function influences expression of methamphetamine-induced behavioral sensitization

• Published in: Scientific reports Vol. 11; no. 1; pp. 24529 - 15
• Main Authors: Calma, I. Daphne, Persons, Amanda L., Napier, T. Celeste
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31.12.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378; 631/378/1689; 692/617; 692/699; Animals; Behavior, Animal - drug effects; Central Nervous System Stimulants - administration & dosage; Central Nervous System Stimulants - adverse effects; Energy requirements; Humanities and Social Sciences; Intravenous administration; Laboratory animals; Locomotion - drug effects; Male; Methamphetamine; Methamphetamine - administration & dosage; Methamphetamine - adverse effects; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Motor Activity - drug effects; multidisciplinary; Rats; Rodents; Rotenone; Rotenone - administration & dosage; Rotenone - adverse effects; Rotenone - analogs & derivatives; Science; Science (multidisciplinary); Self Administration; Time Factors; Titration; Toxins
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-04301-9

Repeated methamphetamine use leads to long lasting brain and behavioral changes in humans and laboratory rats. These changes have high energy requirements, implicating a role for mitochondria. We explored whether mitochondrial function underpins behaviors that occur in rats months after stopping methamphetamine self-administration. Accordingly, rats self-administered intravenous methamphetamine for 3 h/day for 14 days. The mitochondrial toxin rotenone was administered as (1 mg/kg/day for 6 days) via an osmotic minipump starting at 0, 14 or 28 days of abstinence abstinence. On abstinence day 61, expression of methamphetamine-induced behavioral sensitization was obtained with an acute methamphetamine challenge in rotenone-free rats. Rotenone impeded the expression of sensitization, with the most robust effects obtained with later abstinence exposure. These findings verified that self-titration of moderate methamphetamine doses results in behavioral (and thus brain) changes that can be revealed months after exposure termination, and that the meth-initiated processes progressed during abstinence so that longer abstinence periods were more susceptible to the consequences of exposure to a mitochondrial toxin.