title: Signals from the Fourth Dimension Regulate Drug Relapse.
abstract: Despite the enormous societal burden of alcohol and drug addiction and abundant research describing drug-induced maladaptive synaptic plasticity, there are few effective strategies for treating substance use disorders. Recent awareness that synaptic plasticity involves astroglia and the extracellular matrix is revealing new possibilities for understanding and treating addiction. We first review constitutive corticostriatal adaptations that are elicited by and shared between all abused drugs from the perspective of tetrapartite synapses, and integrate recent discoveries regarding cell type-specificity in striatal neurons. Next, we describe recent discoveries that drug-seeking is associated with transient synaptic plasticity that requires all four synaptic elements and is shared across drug classes. Finally, we prognosticate how considering tetrapartite synapses can provide new treatment strategies for addiction.
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA; Department of Psychiatry and Behavioral Sciences, Addiction Sciences Division, Medical University of South Carolina, 67 President Street, Charleston, SC, 29425, USA. Electronic address: mulholl@musc.edu.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Mulholland
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA; Department of Psychiatry and Behavioral Sciences, Addiction Sciences Division, Medical University of South Carolina, 67 President Street, Charleston, SC, 29425, USA.
authors.forename: L Judson
authors.initials: LJ
authors.lastname: Chandler
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA. Electronic address: kalivas@musc.edu.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Kalivas
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D009473:Neuronal Plasticity / Q000502:physiology*; D012008:Recurrence; D019966:Substance-Related Disorders / Q000503:physiopathology* / Q000628:therapy; D013569:Synapses / Q000502:physiology*
keywords: drug addiction; extracellular matrix; synaptic plasticity; tetrapartite synapses