title: Corticostriatal circuitry in regulating diseases characterized by intrusive thinking.
abstract: Intrusive thinking triggers clinical symptoms in many neuropsychiatric disorders. Using drug addiction as an exemplar disorder sustained in part by intrusive thinking, we explore studies demonstrating that impairments in corticostriatal circuitry strongly contribute to intrusive thinking. Neuroimaging studies have long implicated this projection in cue-induced craving to use drugs, and preclinical models show that marked changes are produced at corticostriatal synapses in the nucleus accumbens during a relapse episode. We delineate an accumbens microcircuit that mediates cue-induced drug seeking becoming an intrusive event. This microcircuit harbors many potential therapeutic targets. We focus on preclinical and clinical studies, showing that administering N-acetylcysteine restores uptake of synaptic glutamate by astroglial glutamate transporters and thereby inhibits intrusive thinking. We posit that because intrusive thinking is a shared endophenotype in many disorders, N-acetylcysteine has positive effects in clinical trials for a variety of neuropsychiatric disorders, including drug addiction, gambling, trichotillomania, and depression.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Kalivas
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, USA; Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Kalivas
mesh_terms: D002540:Cerebral Cortex / Q000502:physiology*; D006801:Humans; D001523:Mental Disorders / Q000503:physiopathology* / Q000523:psychology; D009415:Nerve Net / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D019966:Substance-Related Disorders / Q000503:physiopathology* / Q000523:psychology; D013850:Thinking / Q000502:physiology*
keywords: N-acetylcysteine; addiction; corticostriatal; glutamate; intrusive thinking; synaptic plasticity