title: Optogenetic inhibition of dorsal medial prefrontal cortex attenuates stress-induced reinstatement of palatable food seeking in female rats.
abstract: Relapse to maladaptive eating habits during dieting is often provoked by stress. Recently, we identified a role of dorsal medial prefrontal cortex (mPFC) neurons in stress-induced reinstatement of palatable food seeking in male rats. It is unknown whether endogenous neural activity in dorsal mPFC drives stress-induced reinstatement in female rats. Here, we used an optogenetic approach, in which female rats received bilateral dorsal mPFC microinjections of viral constructs coding light-sensitive eNpHR3.0-eYFP or control eYFP protein and intracranial fiber optic implants. Rats were food restricted and trained to lever press for palatable food pellets. Subsequently, pellets were removed, and lever pressing was extinguished; then the effect of bilateral dorsal mPFC light delivery on reinstatement of food seeking was assessed after injections of the pharmacological stressor yohimbine (an α-2 andrenoceptor antagonist) or pellet priming, a manipulation known to provoke food seeking in hungry rats. Dorsal mPFC light delivery attenuated yohimbine-induced reinstatement of food seeking in eNpHR3.0-injected but not eYFP-injected rats. This optical manipulation had no effect on pellet-priming-induced reinstatement or ongoing food-reinforced responding. Dorsal mPFC light delivery attenuated yohimbine-induced Fos immunoreactivity and disrupted neural activity during in vivo electrophysiological recording in awake rats. Optical stimulation caused significant outward currents and blocked electrically evoked action potentials in eNpHR3.0-injected but not eYFP-injected mPFC hemispheres. Light delivery alone caused no significant inflammatory response in mPFC. These findings indicate that intracranial light delivery in eNpHR3.0 rats disrupts endogenous dorsal mPFC neural activity that plays a role in stress-induced relapse to food seeking in female rats.
authors.affiliation: Intramural Research Program, National Institutes of Health/National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. donna.calu@nih.gov
authors.forename: Donna J
authors.initials: DJ
authors.lastname: Calu
authors.forename: Alex B
authors.initials: AB
authors.lastname: Kawa
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Marchant
authors.forename: Brittany M
authors.initials: BM
authors.lastname: Navarre
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Henderson
authors.forename: Billy
authors.initials: B
authors.lastname: Chen
authors.forename: Hau-Jie
authors.initials: HJ
authors.lastname: Yau
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Bossert
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Schoenbaum
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
authors.forename: Brandon K
authors.initials: BK
authors.lastname: Harvey
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Hope
authors.forename: Yavin
authors.initials: Y
authors.lastname: Shaham
mesh_terms: D000818:Animals; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D005108:Extinction, Psychological / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007266:Inhibition, Psychological; D062308:Optogenetics; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D012054:Reinforcement, Psychology; D012646:Self Administration; D013315:Stress, Psychological / Q000503:physiopathology*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D015016:Yohimbine