PT - JOURNAL ARTICLE AU - Claudia Juárez-Portilla AU - Michael Pitter AU - Rachel D. Kim AU - Pooja Y. Patel AU - Robert A. Ledesma AU - Joseph LeSauter AU - Rae Silver TI - Brain Activity during Methamphetamine Anticipation in a Non-Invasive Self-Administration Paradigm in Mice AID - 10.1523/ENEURO.0433-17.2018 DP - 2018 Mar 12 TA - eneuro PG - ENEURO.0433-17.2018 4099 - http://www.eneuro.org/content/early/2018/03/12/ENEURO.0433-17.2018.short 4100 - http://www.eneuro.org/content/early/2018/03/12/ENEURO.0433-17.2018.full AB - The ability to sense time and anticipate events is critical for survival. Learned responses that allow anticipation of the availability of food or water have been intensively studied. While anticipatory behaviors also occur prior to availability of regularly available rewards, there has been relatively little work on anticipation of drugs of abuse, specifically methamphetamine (MA). In the present study, we used a protocol that avoided possible CNS effects of stresses of handling or surgery by testing anticipation of MA availability in animals living in their home cages, with daily voluntary access to the drug at a fixed time of day. Anticipation was operationalized as the amount of wheel running prior to MA availability. Mice were divided into four groups given access to either nebulized MA or water, in early or late day. Animals with access to MA, but not water controls, showed anticipatory activity, with more anticipation in early compared to late day and significant interaction effects. Next, we explored the neural basis of the MA anticipation, using c-FOS expression, in animals euthanized at the usual time of nebulization access. In the dorsomedial hypothalamus and orbitofrontal cortex, the pattern of c-FOS expression paralleled that of anticipatory behavior, with significant main and interaction effects of treatment and time of day. The results for the lateral septum were significant for main effects and marginally significant for interaction effects. These studies suggest that anticipation of MA is associated with activation of brain regions important in circadian timing, emotional regulation and decision-making.Significance Statement A primary function of the brain is to predict future events. Brain regions regulating anticipation of drugs have received little analysis. We studied methamphetamine anticipation in mice living in their home cage and having access to nebulized methamphetamine for 1hr daily via a tunnel to a nebulizing chamber. Mice spontaneously awakened from sleep ∼2hr before methamphetamine availability and voluntarily entered the chamber when accessible. This protocol avoided the potential CNS effects associated with handling, injections and surgery. c-FOS expression before methamphetamine availability was observed in the dorsomedial hypothalamus, lateral septum, and orbitofrontal cortex, suggesting that anticipation of regularly scheduled methamphetamine is associated with activation of brain regions important in circadian timing, emotional regulation and decision-making.