title: Role of Dopamine 2 Receptor in Impaired Drug-Cue Extinction in Adolescent Rats.
abstract: Adolescent drug users display resistance to treatment such as cue exposure therapy (CET), as well as increased liability to relapse. The basis of CET is extinction learning, which involves dopamine signaling in the medial prefrontal cortex (mPFC). This system undergoes dramatic alterations during adolescence. Therefore, we investigated extinction of a cocaine-associated cue in adolescent and adult rats. While cocaine self-administration and lever-alone extinction were not different between the two ages, we observed that cue extinction reduced cue-induced reinstatement in adult but not adolescent rats. Infusion of the selective dopamine 2 receptor (D2R)-like agonist quinpirole into the infralimbic cortex (IL) of the mPFC prior to cue extinction significantly reduced cue-induced reinstatement in adolescents. This effect was replicated by acute systemic treatment with the atypical antipsychotic aripiprazole (Abilify), a partial D2R-like agonist. These data suggest that adolescents may be more susceptible to relapse due to a deficit in cue extinction learning, and highlight the significance of D2R signaling in the IL for cue extinction during adolescence. These findings inspire new tactics for improving adolescent CET, with aripiprazole representing an exciting potential pharmacological adjunct for behavioral therapy.
authors.affiliation: Behavioral Neuroscience Division, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3051, Australia The Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Isabel C
authors.initials: IC
authors.lastname: Zbukvic
authors.affiliation: Behavioral Neuroscience Division, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3051, Australia The Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Despina E
authors.initials: DE
authors.lastname: Ganella
authors.affiliation: Behavioral Neuroscience Division, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3051, Australia The Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Christina J
authors.initials: CJ
authors.lastname: Perry
authors.affiliation: Behavioral Neuroscience Division, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3051, Australia The Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Heather B
authors.initials: HB
authors.lastname: Madsen
authors.affiliation: Behavioral Neuroscience Division, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3051, Australia The Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Bye
authors.affiliation: Behavioral Neuroscience Division, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3051, Australia The Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lawrence
authors.affiliation: Behavioral Neuroscience Division, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3051, Australia The Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D000068180:Aripiprazole / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000378:metabolism*; D003463:Cues; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D007858:Learning / Q000187:drug effects / Q000502:physiology; D008297:Male; D009042:Motivation / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D019257:Quinpirole / Q000494:pharmacology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D012646:Self Administration
chemical_list: D014150:Antipsychotic Agents; C000607792:DRD2 protein, rat; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D000068180:Aripiprazole; D003042:Cocaine
keywords: adolescence; aripiprazole; dopamine; extinction; infralimbic cortex