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    Counteractive effects of antenatal glucocorticoid treatment on D1 receptor modulation of spatial working memory. 
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    Counteractive effects of antenatal glucocorticoid treatment on D1 receptor modulation of spatial working memory.

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    Published version (666.2Kb)
    Volume
    233
    Pagination
    3751 - 3761
    DOI
    10.1007/s00213-016-4405-8
    Journal
    Psychopharmacology (Berl)
    Issue
    21-22
    Metadata
    Show full item record
    Abstract
    RATIONALE: Antenatal exposure to the glucocorticoid dexamethasone dramatically increases the number of mesencephalic dopaminergic neurons in rat offspring. However, the consequences of this expansion in midbrain dopamine (DA) neurons for behavioural processes in adulthood are poorly understood, including working memory that depends on DA transmission in the prefrontal cortex (PFC). OBJECTIVES: We therefore investigated the influence of antenatal glucocorticoid treatment (AGT) on the modulation of spatial working memory by a D1 receptor agonist and on D1 receptor binding and DA content in the PFC and striatum. METHODS: Pregnant rats received AGT on gestational days 16-19 by adding dexamethasone to their drinking water. Male offspring reared to adulthood were trained on a delayed alternation spatial working memory task and administered the partial D1 agonist SKF38393 (0.3-3 mg/kg) by systemic injection. In separate groups of control and AGT animals, D1 receptor binding and DA content were measured post-mortem in the PFC and striatum. RESULTS: SKF38393 impaired spatial working memory performance in control rats but had no effect in AGT rats. D1 binding was significantly reduced in the anterior cingulate cortex, prelimbic cortex, dorsal striatum and ventral pallidum of AGT rats compared with control animals. However, AGT had no significant effect on brain monoamine levels. CONCLUSIONS: These findings demonstrate that D1 receptors in corticostriatal circuitry down-regulate in response to AGT. This compensatory effect in D1 receptors may result from increased DA-ergic tone in AGT rats and underlie the resilience of these animals to the disruptive effects of D1 receptor activation on spatial working memory.
    Authors
    Virdee, K; Kentrop, J; Jupp, B; Venus, B; Hensman, D; McArthur, S; Wilkinson, J; Robbins, TW; Gillies, G; Dalley, JW
    URI
    http://qmro.qmul.ac.uk/xmlui/handle/123456789/17763
    Collections
    • Centre for Oral Immunobiology and Regenerative Medicine [394]
    Language
    eng
    Licence information
    This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Final publication is available at Springer via http://dx.doi.org/10.1007/s00213-016-4405-8
    Copyright statements
    (c) The Author(s) 2016.

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