Neonatal glucocorticoid treatment increased depression-like behaviour in adult rats

Abstract

Synthetic glucocorticoid dexamethasone (DEX) is frequently used as a therapeutic agent to lessen the morbidity of chronic lung disease in premature infants. Previous studies suggested that neonatal DEX treatment altered brain development and cognitive function. It has been recognized that the amygdala is involved in emotional processes and also a critical site of neuronal plasticity for fear conditioning. Little is known about the possible long-term adverse effect of neonatal DEX treatment on amygdala function. The present study was aimed to evaluate the possible effect of neonatal DEX treatment on the synaptic function of amygdala in adult rats. Newborn Wistar rats were subjected to subcutaneous tapering-dose injections of DEX (0.5, 0.3 and 0.1 mg/kg) from post-natal day one to three, PN1-PN3. Animals were then subjected to a forced swimming test (FST) and electrophysiological recording aged eight weeks. The results of the FST showed neonatal DEX treatment increased depression-like behaviour in adulthood. After acute stress evoking, the percentage of time spent free floating is significantly increased in the DEX treated group compared with the control animals. Furthermore, neonatal DEX treatment elevated long-term potentiation (LTP) response and the phosphorylation level of MAPK in the lateral nucleus of amygdala (LA). Intracerebroventricular infusion of the MAPK inhibitor, PD98059, showed significant rescue effects including reduced depression-like behaviour and restoration of LTP to within normal range. In conclusion, our results suggested that MAPK signalling cascade in the LA plays an important role in the adverse effect of neonatal DEX treatment on amygdala function, which may result in adverse consequences in adult age, such as the enhancement of susceptibility for a depressive disorder in later life.

CRH/CRHR1 mediates prenatal synthetic glucocorticoid programming of depression‐like behavior across 2 generations

“…Prior studies have strongly suggested that GCs, which are major mediators of stress, are the major causal agent of MDD (52,53). Many studies have demonstrated that repeated administration of GCs can induce depressive-like behavior in rodents (54,55). In the present study, we showed that prenatal Dex exposure leads to continuous elevation of GC level in circulation even from E18.…”

The novel antidepressant ketamine enhances dentate gyrus proliferation with no effects on synaptic plasticity or hippocampal function in depressive‐like rats

“…Mean immobility over a 5 minutes test period was 50.5 ± 11.0 seconds (SAL/SAL), 47.7 ± 8.4 seconds (SAL/KETA), 49.26 ± 7.5 seconds (DEXA/SAL) and 41.76 ± 10.1 seconds (DEXA/KETA). Our results are similar to those of Ko et al showing effects of pre‐natal dexamethasone on immobility in FST only in situations of acute stress. We observed no detectable sex differences (data not shown).…”

Effect of neonatal dexamethasone treatment on cognitive abilities of adult male mice and gene expression in the hypothalamus

“…Adult rats administered with dexamethasone at high doses on postnatal day 5-10 demonstrate reduced neophobia and anxiety in the Light/Dark Box and the Open Field tests, without change in locomotor activity (Yates et al, 2016). At the same time, administration of dexamethasone at low doses to rats during the first three days of their life can cause increases in anxious behavior (Neal et al, 2004;Vazquez et al, 2012) as well as in depressive-like behavior (Ko et al, 2014;Li et al, 2014b). Or, conversely, it may have no effect on the locomotor activity, anxious and social behavior of rats in adulthood (Kamphuis et al, 2004).…”

“…All injections were administered subcutaneously once a day between 9 am and 10 am. The administration scheme and doses were chosen according to previous research (Kamphuis et al, 2003;Ko et al, 2014;Li et al, 2014a, b).…”

“…Behavioral deficits in animals like these have been well studied by rat experiments. Those animals were shown to have changes in anxious and depression-like behaviour, learning and memory deficits (Kamphuis et al, 2004;Neal et al, 2004;Claessens et al, 2012;Vazquez et al, 2012;Ko et al, 2014). A few works on mice that use the dexamethasone model have revealed changes in anxious behavior and impairment in novel object recognition (Li et al, 2014a).…”