Circuit remodeling driven by pathological forms of synaptic plasticity underlies several psychiatric diseases, including addiction. Deep brain stimulation has been applied to treat a number of neurological and psychiatric conditions, although its effects are transient and mediated by largely unknown mechanisms. Recently, optogenetic methods that restore normal transmission at identified synapses in mice have shown that cocaine-adaptive behavior can be reversed in vivo. The most efficient protocols rely on the activation of metabotropic glutamate receptors, mGluRs, which “depotentiate” excitatory synaptic inputs onto dopamine D1 receptor medium-sized spiny neurons and normalize drug-adaptive behavior. Creed and colleagues show that acute low-frequency deep brain stimulation, refined by selective blockade of dopamine D1 receptors, mimics optogenetic mGluR-dependent normalization of synaptic transmission. A long-lasting abolishment of behavioral sensitization was observed.
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Creed M, Pascoli VJ, Lüscher C: Addiction therapy. Refining deep brain stimulation to emulate optogenetic treatment of synaptic pathology. Science 347(6222): 659-664 (2015).
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http://www.ncbi.nlm.nih.gov/pubmed/25657248