Abstract
RationaleAntenatal 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).ObjectivesWe 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.MethodsPregnant 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.ResultsSKF38393 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.ConclusionsThese 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.
Highlights
Stress during critical periods of development has widely recognised detrimental effects on maturing neuronal populations in the brain with implications for the aetiology of various clinical disorders (Gillies et al 2014; Slotkin et al 2006; Spear 2000)
D1 binding was significantly reduced in the anterior cingulate cortex, prelimbic cortex, dorsal striatum and ventral pallidum of antenatal glucocorticoid treatment (AGT) rats compared with control animals
These findings demonstrate that D1 receptors in corticostriatal circuitry down-regulate in response to AGT
Summary
Stress during critical periods of development has widely recognised detrimental effects on maturing neuronal populations in the brain with implications for the aetiology of various clinical disorders (Gillies et al 2014; Slotkin et al 2006; Spear 2000). PFC-dependent functions depend on the local level of D1 receptor activation with low and high levels of D1 receptor stimulation impairing cognitive performance (Granon et al 2000; Mizoguchi et al 2009; Sawaguchi and Goldman-Rakic 1991; Verma and Moghaddam 1996; Zahrt et al 1997) Such findings suggest an underlying U-shaped function, consistent with the proposed role of DA acting on D1 receptors in modulating the spatial tuning properties of PFC neurons (Sawaguchi et al 1988; Vijayraghavan et al 2007; Williams and Goldman-Rakic 1995; Yang and Seamans 1996). These findings accord with the view that the PFC is modulated by stress and arousal through D1 receptor-dependent mechanisms (Robbins and Arnsten 2009)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
