RETRACTED: Maternal adversity, glucocorticoids and programming of neuroendocrine function and behaviour

The Size and Distribution of Midbrain Dopaminergic Populations are Permanently Altered by Perinatal Glucocorticoid Exposure in a Sex- Region- and Time-Specific Manner

“…It should therefore be considered whether the effects of perinatal GC exposure could be secondary to changes in the prevailing adult levels of the adrenal steroid. Importantly, however, maternal GC treatment appears to have opposite effects on basal and stimulated GC levels in adult males and females, and qualitative differences have been reported for HPA axis activity after pre-and neonatal GC exposure (Weinstock, 2001;Kamphuis et al, 2003;Owen et al, 2005). Thus it is unlikely that these contrasting effects on the HPA axis can be causative for the qualitatively similar effects of both our treatment regimens on the adult midbrain DA populations.…”

“…It is known that physiological levels of GCs augment DA activity in the striatum (Piazza et al, 1996a) and evidence suggests that perinatal exposure to synthetic GCs alters the responsiveness of the adult HPA axis (Weinstock, 2001;Owen et al, 2005). It should therefore be considered whether the effects of perinatal GC exposure could be secondary to changes in the prevailing adult levels of the adrenal steroid.…”

“…Among other factors, endogenous glucocorticoid (GC) hormones released in response to stressors, either by the fetal or maternal hypothalamopituitary-adrenal (HPA) axis, are thought to play an important role in neurobiological programming in humans and many experimental species (Weinstock, 2001;Owen et al, 2005;Van den Bergh et al, 2005). For example, in the rat, prenatal GC treatment and exposure to stress similarly alter adult expression of the GC receptors (GRs) in brain regions that are important in regulating negative feedback within the HPA axis, resulting in permanent changes in circulating corticosterone levels (Barbazanges et al, 1996;Weinstock, 2001;Owen et al, 2005). It is also increasingly evident that early exposure to GCs, as well as stressors, has marked effects on animal and human affective and neuromotor behaviors and cognition (Yeh et al, 2004;Owen et al, 2005;Van den Bergh et al, 2005).…”

“…For example, in the rat, prenatal GC treatment and exposure to stress similarly alter adult expression of the GC receptors (GRs) in brain regions that are important in regulating negative feedback within the HPA axis, resulting in permanent changes in circulating corticosterone levels (Barbazanges et al, 1996;Weinstock, 2001;Owen et al, 2005). It is also increasingly evident that early exposure to GCs, as well as stressors, has marked effects on animal and human affective and neuromotor behaviors and cognition (Yeh et al, 2004;Owen et al, 2005;Van den Bergh et al, 2005). However, there is little direct evidence to relate the consequences of perinatal GC exposure to enduring changes in specific, phenotypically identified, central neurotransmitter populations.…”

“…Hence, we have extended our investigations throughout the rostro-caudal extent of the adult SNc and VTA in order to assess effects on the volume and shape of these regions as well as the size and distribution of the DA populations and the size of the individual perikarya after brief exposure prenatally or neonatally to dexamethasone. The need to study both periods of exposure is governed by the knowledge that different outcomes have been reported for pre-and neonatal GC programming of the neuroendocrine axes governing the stress response and prolactin secretion Owen et al, 2005;Theogaraj et al, 2005;McArthur et al, 2006a) as well as behaviors and indicies of neurotransmitter signaling in the cerebral cortex and hippocampus Kreider et al, 2005;Owen et Moreover, many of these changes are sex-specific, and we have shown that GC programming effects on the DA population size in the hypothalamic arcuate nucleus are restricted to females (McArthur et al, 2006a). Therefore, the present investigations have been carried out in both males and females in order to investigate whether males and females are differentially affected by GC programming effects within the midbrain DA populations.…”