Archives
In this study our result suggests that
In this study, our result suggests that exogenous GR agonist DEX and GR inhibitor RU486 can affect dopaminergic neurotransmitters in the brain. Pituitary adenylate cyclase-activating polypeptide (PACAP), an endogenous neuropeptide, can regulate the synthesis and release of catecholamine. McArthur et al. (2005) noticed that exogenous GR agonist dexamethasone could promote PACAP mRNA transcription, cell proliferation and DA synthesis, but an GR antagonist RU486 does the opposite. It is reported that tyrosine hydroxylase (TH) is the key enzyme of DA synthesis, and its activity is connected to the production of monoamine neurotransmitter. Hagerty et al. (2001) gave low-dose GR agonist DEX to rats in late pregnancy(16–19d) and found that there was an increase of TH positive nisoldipine mg in the offspring. The combination of GR complex and the glucocorticoid response element (GRE) of 5′-flanking region (-2435)GGCACAGTGTGGTCT(-2421) could improve the transcriptional activity of relevant gene, and promote TH expression and DA production. Monoamine oxidase is the main metabolism enzyme of oxidative deamination of monoamine and is vital to the inactivation of monoamine neurotransmitters (Radcliffe et al., 2009). It has beenr reported that corticosterone is able to downgrade rapidly the expression of MAO-A mRNA in hippocampal sub-regions, and this effect can be reversed by RU484, a glucocorticoid receptor antagonist, demonstrating that corticosterone can regulate the synthesis of MAO-A by GR specific transcription (Morsink et al., 2007). The biological function of DA is exerted through DRD, and the affinity between DRD and DA as well as its own expression can affect DA biological function. Our results are partially in accordance with a study by Wróbel et al. (2004), which observed a reduction of D2 receptor in the striatum after injecting male Swiss Albino mice with dexamethasone 4, 8, 16mg/kg for 14days.
The SHR, isolated from Wistar Kyoto (WKY) rats by selective inbreeding, is most widely used animal model for ADHD. Our study demonstrated that the line crossing and rearing of SHR rats were significantly enhanced after treatment with DEX. The behavior of SHR was consistent with the clinical features of ADHD. Y maze test indicated that the correct response rate of SHR in DEX group increased progressively comparing with that before treatment, while RU486 group and CON group had no evident differences before and after treatment (0.05). The performances of behavior test of rats in DEX group were much better than those in CON group. The interaction between the two elements had also significant difference (P<0.05). Main e
ffect of animal model factors>main effect of drug-intervention factors (0.05); the interaction between the two elements had also significant difference (0.01). This implies that GR agonist DEX can improve the symptom of hyperactivity and attention deficit in rats.
In this study, we found that the levels of DA and NE in the prefrontal cortex and the striatum of SHR was changed after treatment. The results demonstrated that DEX could increase the level of DA in the prefrontal cortex of SHR as well as the levels of DA and NE in the striatum. The levels of DA in the prefrontal cortex of WKY and CON groups showed no changes after treatment, with exception that the expression of DA was increased in the striatum of WKY rats after treatment. In between the prefrontal cortex and the striatum, the interaction between the two elements had also significant difference (0.05). The interaction between the two elements had also significant difference (P<0.01). In the prefrontal cortex, main effect of animal model factors