Endocrine Abstracts

By including the synthetic glucocorticoid (GC), dexamethasone, in the maternal drinking water on gestational days 16–19 (0.5 μg/ml) or days 1–7 after birth (1.0 μg/ml), we have recently demonstrated (McArthur et al. J. Neuroendocrinol. 17: 475) that perinatal exposure of rat pups to GCs increased dopaminergic (DA) cell numbers in the adult ventral tegmental area (VTA) at −5.1 to −5.4 mm relative to Bregma (level I). In order to investigate whether this could be due to an effect on the positioning of the neurones throughout the entire nucleus, further counts of tyrosine hydroxylase immunopositive cells (TH-IR) at levels II and III (−5.4 to −5.7 mm and −5.7 to −6.0 mm) were made, along with measurement of the nucleus volume at each level using the Cavalieri principle. Our results in the female offspring showed that perinatal GCs significantly increased TH-IR cell number at all levels of the VTA and volume at level III compared with the offspring of control dams receiving normal drinking water (P<0.05), but effects were more pronounced with prenatal vs. neonatal treatment for cell number (50% increase at levels I-III vs. 60% at level I and 30% at levels I and III, respectively) and volume (100% vs. 50% increase at level III respectively). As the total number of neurones (NeuN immunostaining) at all levels did not change with either treatment regime, the data suggest that perinatal GC exposure alters expression of the adult DA phenotype rather than the positioning of cells within the nucleus. The data also demonstrate that the overall volume and shape of the nucleus is profoundly influenced by perinatal GC exposure. The VTA is the origin of the mesocorticolimbic DA system which is involved in processes related to motivation, reward and cognition, and its dysregulation is implicated in the pathophysiology of major psychoses, such as schizophrenia, attention deficit-hyperactivity disorder and addictive behaviours. The ability of early GCs to produce a disordered cytoarchitecture of the adult nucleus thus has significance for the increasing use of GCs in perinatal medicine.

Acknowledgement: The work was supported by The Wellcome Trust.