title: Optogenetically-induced tonic dopamine release from VTA-nucleus accumbens projections inhibits reward consummatory behaviors.
abstract: Recent optogenetic studies demonstrated that phasic dopamine release in the nucleus accumbens may play a causal role in multiple aspects of natural and drug reward-related behaviors. The role of tonic dopamine release in reward consummatory behavior remains unclear. The current study used a combinatorial viral-mediated gene delivery approach to express ChR2 on mesolimbic dopamine neurons in rats. We used optical activation of this dopamine circuit to mimic tonic dopamine release in the nucleus accumbens and to explore the causal relationship between this form of dopamine signaling within the ventral tegmental area (VTA)-nucleus accumbens projection and consumption of a natural reward. Using a two bottle choice paradigm (sucrose vs. water), the experiments revealed that tonic optogenetic stimulation of mesolimbic dopamine transmission significantly decreased reward consummatory behaviors. Specifically, there was a significant decrease in the number of bouts, licks and amount of sucrose obtained during the drinking session. Notably, activation of VTA dopamine cell bodies or dopamine terminals in the nucleus accumbens resulted in identical behavioral consequences. No changes in water intake were evident under the same experimental conditions. Collectively, these data demonstrate that tonic optogenetic stimulation of VTA-nucleus accumbens dopamine release is sufficient to inhibit reward consummatory behavior, possibly by preventing this circuit from engaging in phasic activity that is thought to be essential for reward-based behaviors.
authors.affiliation: Department of Neurobiology and Anatomy, Wake Forest School of Medicine, Winston-Salem, NC, USA; Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Mikhailova
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Bass
authors.affiliation: Department of Neurobiology and Anatomy, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Valentina P
authors.initials: VP
authors.lastname: Grinevich
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Chappell
authors.affiliation: Department of Neurobiology and Anatomy, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Alex L
authors.initials: AL
authors.lastname: Deal
authors.affiliation: Department of Physics, Wake Forest University, Winston-Salem, NC, USA.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Bonin
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Jeff L
authors.initials: JL
authors.lastname: Weiner
authors.affiliation: Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia.
authors.forename: Raul R
authors.initials: RR
authors.lastname: Gainetdinov
authors.affiliation: Department of Neurobiology and Anatomy, Wake Forest School of Medicine, Winston-Salem, NC, USA; Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia. Electronic address: ebudygin@wakehealth.edu.
authors.forename: Evgeny A
authors.initials: EA
authors.lastname: Budygin
mesh_terms: D000818:Animals; D002755:Choice Behavior / Q000502:physiology; D003259:Consummatory Behavior / Q000502:physiology; D019422:Dietary Sucrose; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism; D060766:Drinking Water; D004558:Electric Stimulation; D005247:Feeding Behavior / Q000502:physiology* / Q000523:psychology; D008297:Male; D009714:Nucleus Accumbens / Q000166:cytology / Q000378:metabolism*; D062308:Optogenetics; D010507:Periodicity; D020318:Rats, Long-Evans; D012201:Reward; D017557:Ventral Tegmental Area / Q000378:metabolism*
chemical_list: D019422:Dietary Sucrose; D060766:Drinking Water; D004298:Dopamine
keywords: VTA; nucleus accumbens; optogenetics; reward; tonic dopamine