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• W2051211720 abstract "The striatum receives prominent dopaminergic innervation that is integral to appetitive learning, performance, and motivation. Signaling through the dopamine D₂ receptor is critical for all of these processes. For instance, drugs with high affinity for the D₂ receptor potently alter timing of operant responses and modulate motivation. Recently, in an attempt to model a genetic abnormality encountered in schizophrenia, mice were generated that reversibly overexpress D₂ receptors specifically in the striatum (Kellendonk et al., 2006). These mice have impairments in working memory and behavioral flexibility, components of the cognitive symptoms of schizophrenia, that are not rescued when D₂ overexpression is reversed in the adult. Here we report that overexpression of striatal D₂ receptors also profoundly affects operant performance, a potential index of negative symptoms. Mice overexpressing D₂ exhibited impairments in the ability to time food rewards in an operant interval timing task and reduced motivation to lever press for food reward in both the operant timing task and a progressive ratio schedule of reinforcement. The motivational deficit, but not the timing deficit, was rescued in adult mice by reversing D₂ overexpression with doxycycline. These results suggest that early D₂ overexpression alters the organization of interval timing circuits and confirms that striatal D₂ signaling in the adult regulates motivational process. Moreover, overexpression of D₂ under pathological conditions such as schizophrenia and Parkinson9s disease could give rise to motivational and timing deficits." @default.
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• W2051211720 date "2007-07-18" @default.
• W2051211720 modified "2023-10-12" @default.
• W2051211720 title "Transient Overexpression of Striatal D2 Receptors Impairs Operant Motivation and Interval Timing" @default.
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• W2051211720 doi "https://doi.org/10.1523/jneurosci.1736-07.2007" @default.
• W2051211720 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6672869" @default.
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