Journal
FRONTIERS IN NEUROSCIENCE
Volume 16, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fnins.2022.1064369
Keywords
attention deficit hyperactivity disorder; glucocorticoid receptor; 5-HT; 5-HT1A receptor; 5-HT2A receptor
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The study investigates the alterations of the central 5-HT system in spontaneously hypertensive rats (SHR) and the correlation with SHR behaviors, as well as the effects of glucocorticoid intervention. Results show that the down-regulation of 5-HT and 5-HT2AR expressions and the up-regulation of 5-HT1AR in the prefrontal cortex of ADHD rats suggest a dysfunctional 5-HT system in ADHD. Glucocorticoid receptor agonist can upregulate the expression of 5-HT and 5-HT2AR and downregulate the expression of 5-HT1AR, reducing hyperactivity and attention deficit behavior in SHR.
ObjectiveThis work is to investigate the alterations of the central 5-hydroxytryptamine (5-HT) system in spontaneously hypertensive rats (SHR) and the correlation with the behaviors of SHR, and to explore the effects of glucocorticoid intervention on the central 5-HT system and SHR behaviors. Materials and methodsThree weeks old SHR were chosen as the attention-deficit hyperactivity disorder (ADHD) model and treated with glucocorticoid receptor (GR) agonist or inhibitor, whereas Wista Kyoto rats (WKY) were chosen as the normal control group. Open-field test and Lat maze test were used to evaluate the spontaneous activities and non-selective attention. The levels of 5-HT in the extracellular fluid specimens of the prefrontal cortex of rats were analyzed by high-performance liquid chromatography. The expressions of GR, 5-HT1A receptor (5-HT1AR), and 5-HT2A receptor (5-HT2AR) in the prefrontal cortex were analyzed through immunohistochemistry. ResultsOur study demonstrated that the 5-HT level was lower in the prefrontal cortex of SHR compared to that of WKY. The Open-field test and Lat maze test showed that GR agonist (dexamethasone, DEX) intervention ameliorated attention deficit and hyperactive behavior, whereas GR inhibitor (RU486) aggravated the disorders. With DEX, the expression levels of 5-HT and 5-HT2AR in the prefrontal cortex of SHR were significantly higher than those in the control group, whereas the expression level of 5-HT1AR was lower. However, the expression levels of 5-HT and 5-HT2AR were significantly decreased after the intervention with RU486, while the expression level of 5-HT1AR increased. Results showed that glucocorticoid was negatively correlated with 5-HT1AR and positively correlated with 5-HT2AR. ConclusionIn the prefrontal cortex of ADHD rats, the down-regulation of 5-HT and 5-HT2AR expressions and the up-regulation of 5-HT1AR, compared with WYK rats, suggested a dysfunctional central 5-HT system in ADHD rats. The GR agonist can upregulate the expression of 5-HT and 5-HT2AR and downregulate the expression of 5-HT1AR in the prefrontal cortex of SHR as well as reduce the hyperactivity and attention deficit behavior in SHR, while the opposite was true for the GR inhibitor. It is suggested that the dysfunction of the 5-HT system in ADHD rats is closely related to glucocorticoid receptor activity.
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