Mitochondrial Function Influences Expression of Methamphetamine-Induced Motor Sensitization

Abstract Repeated methamphetamine use leads to neuronal maladaptations resulting in addictions. Mechanisms that underpin such adaptations have high energy requirements, implicating mitochondria involvement in addiction-related processes. We pharmacologically explored this possibility in methamphetamine self-administering rats. Motor sensitization a readout that is thought to reflect brain maladaptations akin to those occurring in methamphetamine abusing humans. This was assessed to determine (i) if a short access self-administration protocol results in the expression of motor sensitization, (iii) if and when, mitochondrial function is critical for protracted maintenance and (iii) whether drug contingency influences motor sensitization. Rats self-administered iv methamphetamine for 3 hours per day for 14 days. Those with iv cannula that failed patency were redeployed as non-contingent methamphetamine-matched animals. At three different times during forced abstinence, mitochondrial function was impaired with a low dose of the toxin, rotenone (1mg/kg/day) via a osmotic minipump. Motor sensitization was determined during an acute treatment of methamphetamine (1.25mg/kg sc) on abstinence day 62. Methamphetamine self-administration was sufficient to induce motor sensitization. Rotenone administration prevented the expression of sensitization, but the profile depended on abstinence time exposure. Drug contingency also influenced sensitization profiles. Mitochondrial function underpins neuronal plasticity associated with maintenance of motor sensitization induced by methamphetamine self-administration.