title: Endocannabinoids shape accumbal encoding of cue-motivated behavior via CB1 receptor activation in the ventral tegmentum.
abstract: Transient increases in nucleus accumbens (NAc) dopamine concentration are observed when animals are presented with motivationally salient stimuli and are theorized to energize reward seeking. They arise from high-frequency firing of dopamine neurons in the ventral tegmental area (VTA), which also results in the release of endocannabinoids from dopamine cell bodies. In this context, endocannabinoids are thought to regulate reward seeking by modulating dopamine signaling, although a direct link has never been demonstrated. To test this, we pharmacologically manipulated endocannabinoid neurotransmission in the VTA while measuring transient changes in dopamine concentration in the NAc during reward seeking. Disrupting endocannabinoid signaling dramatically reduced, whereas augmenting levels of the endocannabinoid 2-arachidonoylglycerol (2AG) increased, cue-evoked dopamine concentrations and reward seeking. These data suggest that 2AG in the VTA regulates reward seeking by sculpting ethologically relevant patterns of dopamine release during reward-directed behavior.
authors.affiliation: Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Erik B
authors.initials: EB
authors.lastname: Oleson
authors.forename: Michael V
authors.initials: MV
authors.lastname: Beckert
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Morra
authors.forename: Carien S
authors.initials: CS
authors.lastname: Lansink
authors.forename: Roger
authors.initials: R
authors.lastname: Cachope
authors.forename: Rehab A
authors.initials: RA
authors.lastname: Abdullah
authors.forename: Amy L
authors.initials: AL
authors.lastname: Loriaux
authors.forename: Dustin
authors.initials: D
authors.lastname: Schetters
authors.forename: Tommy
authors.initials: T
authors.lastname: Pattij
authors.forename: Mitchell F
authors.initials: MF
authors.lastname: Roitman
authors.forename: Aron H
authors.initials: AH
authors.lastname: Lichtman
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Cheer
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001522:Behavior, Animal / Q000502:physiology*; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D003463:Cues; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons; D063388:Endocannabinoids; D005989:Glycerides / Q000378:metabolism; D008297:Male; D009042:Motivation; D009474:Neurons / Q000378:metabolism; D009714:Nucleus Accumbens / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D012201:Reward; D017557:Ventral Tegmental Area / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D043884:Receptor, Cannabinoid, CB1; C094503:glyceryl 2-arachidonate; D004298:Dopamine