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TitleThe motivational drive to natural rewards is modulated by prenatal glucocorticoid exposure
Author(s)Cunha, Carina Isabel Soares da
Coimbra, Bárbara Guimarães Salazar
Borges, Sónia Maria de Sousa
Carvalho, Miguel M.
Rodrigues, Ana João
Sousa, Nuno
Issue date2014
PublisherPalgrave Macmillan
JournalTranslational Psychiatry
CitationTransl Psychiatry (2014) 4, e397; doi:10.1038/tp.2014.45
Abstract(s)Exposure to elevated levels of glucocorticoids (GCs) during neurodevelopment has been identified as a triggering factor for the development of reward-associated disorders in adulthood. Disturbances in the neural networks responsible for the complex processes that assign value to rewards and associated stimuli are critical for disorders such as depression, obsessive–compulsive disorders, obesity and addiction. Essential in the understanding on how cues influence behavior is the Pavlovian–instrumental transfer (PIT), a phenomenon that refers to the capacity of a Pavlovian stimulus that predicts a reward to elicit instrumental responses for that same reward. Here, we demonstrate that in utero exposure to GCs (iuGC) impairs both general and selective versions of the PIT paradigm, suggestive of deficits in motivational drive. The iuGC animals presented impaired neuronal activation pattern upon PIT performance in cortical and limbic regions, as well as morphometric changes and reduced levels of dopamine in prefrontal and orbitofrontal cortices, key regions involved in the integration of Pavlovian and instrumental stimuli. Normalization of dopamine levels rescued this behavior, a process that relied on D2/D3, but not D1, dopamine receptor activation. In summary, iuGC exposure programs the mesocorticolimbic dopaminergic circuitry, leading to a reduction in the attribution of the incentive salience to cues, in a dopamine-D2/D3-dependent manner. Ultimately, these results are important to understand how GCs bias incentive processes, a fact that is particularly relevant for disorders where differential attribution of incentive salience is critical.
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AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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