title: Addiction therapy. Refining deep brain stimulation to emulate optogenetic treatment of synaptic pathology.
abstract: Circuit remodeling driven by pathological forms of synaptic plasticity underlies several psychiatric diseases, including addiction. Deep brain stimulation (DBS) 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 protocols that restore normal transmission at identified synapses in mice have provided proof of the idea that cocaine-adaptive behavior can be reversed in vivo. The most efficient protocol relies on the activation of metabotropic glutamate receptors, mGluRs, which depotentiates excitatory synaptic inputs onto dopamine D1 receptor medium-sized spiny neurons and normalizes drug-adaptive behavior. We discovered that acute low-frequency DBS, refined by selective blockade of dopamine D1 receptors, mimics optogenetic mGluR-dependent normalization of synaptic transmission. Consequently, there was a long-lasting abolishment of behavioral sensitization.
authors: Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland.
authors: Meaghan
authors: M
authors: Creed
authors: Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland.
authors: Vincent Jean
authors: VJ
authors: Pascoli
authors: Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland. Service of Neurology, Department of Clinical Neurosciences, University Hospital of Geneva, Geneva, Switzerland. christian.luscher@unige.ch.
authors: Christian
authors: C
authors: Lüscher
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000503:physiopathology / Q000628:therapy*; D003042:Cocaine / Q000008:administration & dosage / Q000009:adverse effects*; D019970:Cocaine-Related Disorders / Q000503:physiopathology / Q000628:therapy*; D046690:Deep Brain Stimulation / Q000379:methods*; D036881:Long-Term Synaptic Depression; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity; D062308:Optogenetics / Q000379:methods*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission
chemical_list: D017447:Receptors, Dopamine D1; D003042:Cocaine