Journal article
Male DAT Val559 Mice Exhibit Compulsive Behavior under Devalued Reward Conditions Accompanied by Cellular and Pharmacological Changes
Cells (Basel, Switzerland), Vol.11(24), p.4059
12/01/2022
DOI: 10.3390/cells11244059
PMCID: PMC9777203
PMID: 36552823
Abstract
Identified across multiple psychiatric disorders, the dopamine (DA) transporter (DAT) Ala559Val substitution triggers non-vesicular, anomalous DA efflux (ADE), perturbing DA neurotransmission and behavior. We have shown that DAT Val559 mice display a waiting impulsivity and changes in cognitive performance associated with enhanced reward motivation. Here, utilizing a within-subject, lever-pressing paradigm designed to bias the formation of goal-directed or habitual behavior, we demonstrate that DAT Val559 mice modulate their nose poke behavior appropriately to match context, but demonstrate a perseverative checking behavior. Although DAT Val559 mice display no issues with the cognitive flexibility required to acquire and re-learn a visual pairwise discrimination task, devaluation of reward evoked habitual reward seeking in DAT Val559 mutants in operant tasks regardless of reinforcement schedule. The direct DA agonist apomorphine also elicits locomotor stereotypies in DAT Val559, but not WT mice. Our observation that dendritic spine density is increased in the dorsal medial striatum (DMS) of DAT Val559 mice speaks to an imbalance in striatal circuitry that might underlie the propensity of DAT Val559 mutants to exhibit compulsive behaviors when reward is devalued. Thus, DAT Val559 mice represent a model for dissection of how altered DA signaling perturbs circuits that normally balance habitual and goal-directed behaviors.
Details
- Title: Subtitle
- Male DAT Val559 Mice Exhibit Compulsive Behavior under Devalued Reward Conditions Accompanied by Cellular and Pharmacological Changes
- Creators
- Adele Stewart - Florida Atlantic UniversityGwynne L Davis - Florida Atlantic UniversityLorena B Areal - Florida Atlantic UniversityMaximilian J Rabil - Florida Atlantic UniversityVuong Tran - Florida Atlantic UniversityFelix P Mayer - Florida Atlantic UniversityRandy D Blakely - Florida Atlantic University
- Resource Type
- Journal article
- Publication Details
- Cells (Basel, Switzerland), Vol.11(24), p.4059
- DOI
- 10.3390/cells11244059
- PMID
- 36552823
- PMCID
- PMC9777203
- NLM abbreviation
- Cells
- ISSN
- 2073-4409
- eISSN
- 2073-4409
- Grant note
- MH086530 / NIMH NIH HHS MH107132 / NIMH NIH HHS
- Language
- English
- Date published
- 12/01/2022
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984618513602771
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