Induction of a hyperanxious state by antenatal dexamethasone: a case for less detrimental natural corticosteroids.
BACKGROUND
Synthetic glucocorticoids are commonly prescribed during pregnancy, despite a lack of systematic investigations of their potential impact on the developing brain and neurological and behavioral performance.


METHODS
Neuroendocrine parameters and behavior in the adult offspring of pregnant Wistar rats treated antenatally with either dexamethasone (DEX) or corticosterone (CORT) were monitored; DEX (.1 mg/kg and 1 mg/kg) and CORT (25 mg/kg) were given to pregnant rat dams on gestation days 18 and 19.


RESULTS
Despite normal basal levels of corticosterone, the adult offspring of mothers given DEX or CORT displayed abnormal responses in the dexamethasone-suppression test. Neither treatment influenced spatial memory performance, but both DEX and CORT facilitated development of depression-like behavior following chronic stress. The latter finding demonstrates that high-dose antenatal corticotherapy can impair the organism's resilience to stress in adulthood. Interestingly, comparison of the progeny of CORT-treated and DEX-treated mothers revealed that the latter were more anxious.


CONCLUSIONS
Since DEX and CORT differ in their affinity for glucocorticoid and mineralocorticoid receptors and corticosteroid-binding globulin, our findings emphasize the need to consider the pharmacologic properties of antenatal corticotherapies and demonstrate the potential long-term benefits of ligands that can bind to both receptors.
Oliveira
Mário
M
Neuroscience Group, Life and Health Science Research Institute, University of Minho, Braga, Portugal.
Bessa
João M
JM
Mesquita
Ana
A
Tavares
Hugo
H
Carvalho
André
A
Silva
Rui
R
Pêgo
José M
JM
Cerqueira
João J
JJ
Palha
Joana A
JA
Almeida
Osborne F X
OF
Sousa
Nuno
N
D000305:Adrenal Cortex Hormones / Q000097:blood / Q000633:toxicity*; D000367:Age Factors; D000818:Animals; D001008:Anxiety Disorders / Q000097:blood / Q000139:chemically induced*; D001522:Behavior, Animal; D001724:Birth Weight / Q000187:drug effects; D003863:Depression / Q000139:chemically induced; D003907:Dexamethasone / Q000097:blood / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D006380:Helplessness, Learned; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D008426:Maternal Deprivation; D008568:Memory / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D013037:Spatial Behavior / Q000187:drug effects
D000305:Adrenal Cortex Hormones; D003907:Dexamethasone