The Impact of Morphine on the Diurnal Variation of Protein Expression in the Dorsal Striatum

A severely understudied area of substance use and abuse disorders is the role of sleep and circadian rhythm processes in the etiology and progression of these disorders. Alterations to sleep wake-cycles or disruptions to circadian rhythms are a hallmark of patients with mood and addiction disorders, yet an understanding of the biological mechanisms underlying this relationship are incomplete. Basic and clinical research indicates circadian rhythms in drug sensitivity and disruptions to the circadian system via environmental and/or genetic perturbation may increase the vulnerability to addiction, while chronic drug use can also lead to sleep and/or circadian disruptions that may persist for years into abstinence and potentially contribute to subsequent relapses. We, along with other laboratories, have demonstrated that circadian disruptions can alter the molecular clock in various brain areas associated with reward and motivation. A major region of convergence for mood and reward related circuitry and a key substrate for drug reward and addiction is the striatum. In particular, the ventral and dorsal striatum is associated with drug reward and the transition to compulsive drug-seeking and habit formation, respectively. Recently, we identified global protein changes across different times of day (i.e., diurnal) in the ventral striatum in mice following chronic administration of morphine. Our project will extend these findings by characterizing the protein changes in the dorsal striatum following morphine across different times of day. We will then compare the diurnal patterns of protein expression between ventral and dorsal striatum at baseline (control) and following morphine to identify region specific diurnal changes by opioids.