title: Designer receptors show role for ventral pallidum input to ventral tegmental area in cocaine seeking.
abstract: The ventral pallidum is centrally positioned within mesocorticolimbic reward circuits, and its dense projection to the ventral tegmental area (VTA) regulates neuronal activity there. However, the ventral pallidum is a heterogeneous structure, and how this complexity affects its role within wider reward circuits is unclear. We found that projections to VTA from the rostral ventral pallidum (RVP), but not the caudal ventral pallidum (CVP), were robustly Fos activated during cue-induced reinstatement of cocaine seeking--a rat model of relapse in addiction. Moreover, designer receptor-mediated transient inactivation of RVP neurons, their terminals in VTA or functional connectivity between RVP and VTA dopamine neurons blocked the ability of drug-associated cues (but not a cocaine prime) to reinstate cocaine seeking. In contrast, CVP neuronal inhibition blocked cocaine-primed, but not cue-induced, reinstatement. This double dissociation in ventral pallidum subregional roles in drug seeking is likely to be important for understanding the mesocorticolimbic circuits underlying reward seeking and addiction.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Mahler
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Elena M
authors.initials: EM
authors.lastname: Vazey
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Jacob T
authors.initials: JT
authors.lastname: Beckley
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Colby R
authors.initials: CR
authors.lastname: Keistler
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: McGlinchey
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kaufling
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, School of Medicine, University of South Carolina, Columbia, South Carolina, USA.
authors.forename: Steven P
authors.identifier: 000000018778946X
authors.initials: SP
authors.lastname: Wilson
authors.affiliation: Department of Bioengineering and Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Woodward
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Aston-Jones
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism*; D003463:Cues; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D012008:Recurrence; D012201:Reward; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
chemical_list: D011954:Receptors, Dopamine; D003042:Cocaine