title: Neonatal amygdala lesions lead to increased activity of brain CRF systems and hypothalamic-pituitary-adrenal axis of juvenile rhesus monkeys.
abstract: The current study examined the long-term effects of neonatal amygdala (Neo-A) lesions on brain corticotropin-releasing factor (CRF) systems and hypothalamic-pituitary-adrenal (HPA) axis function of male and female prepubertal rhesus monkeys. At 12-months-old, CSF levels of CRF were measured and HPA axis activity was characterized by examining diurnal cortisol rhythm and response to pharmacological challenges. Compared with controls, Neo-A animals showed higher cortisol secretion throughout the day, and Neo-A females also showed higher CRF levels. Hypersecretion of basal cortisol, in conjunction with blunted pituitary-adrenal responses to CRF challenge, suggest HPA axis hyperactivity caused by increased CRF hypothalamic drive leading to downregulation of pituitary CRF receptors in Neo-A animals. This interpretation is supported by the increased CRF CSF levels, suggesting that Neo-A damage resulted in central CRF systems overactivity. Neo-A animals also exhibited enhanced glucocorticoid negative feedback, as reflected by an exaggerated cortisol suppression following dexamethasone administration, indicating an additional effect on glucocorticoid receptor (GR) function. Together these data demonstrate that early amygdala damage alters the typical development of the primate HPA axis resulting in increased rather than decreased activity, presumably via alterations in central CRF and GR systems in neural structures that control its activity. Thus, in contrast to evidence that the amygdala stimulates both CRF and HPA axis systems in the adult, our data suggest an opposite, inhibitory role of the amygdala on the HPA axis during early development, which fits with emerging literature on "developmental switches" in amygdala function and connectivity with other brain areas.
authors.affiliation: Departments of Psychology, and Yerkes National Primate Research Center, Atlanta, Georgia 30329 jraper@emory.edu.
authors.forename: Jessica
authors.initials: J
authors.lastname: Raper
authors.affiliation: Departments of Psychology, and Yerkes National Primate Research Center, Atlanta, Georgia 30329.
authors.forename: Shannon B Z
authors.initials: SB
authors.lastname: Stephens
authors.affiliation: Yerkes National Primate Research Center, Atlanta, Georgia 30329.
authors.forename: Amy
authors.initials: A
authors.lastname: Henry
authors.affiliation: Yerkes National Primate Research Center, Atlanta, Georgia 30329.
authors.forename: Trina
authors.initials: T
authors.lastname: Villarreal
authors.affiliation: Departments of Psychology, and Yerkes National Primate Research Center, Atlanta, Georgia 30329.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Bachevalier
authors.affiliation: Departments of Psychology, and Yerkes National Primate Research Center, Atlanta, Georgia 30329.
authors.forename: Kim
authors.initials: K
authors.lastname: Wallen
authors.affiliation: Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia 30322, and Yerkes National Primate Research Center, Atlanta, Georgia 30329.
authors.forename: Mar M
authors.initials: MM
authors.lastname: Sanchez
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000679:Amygdala / Q000293:injuries* / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002940:Circadian Rhythm; D003346:Corticotropin-Releasing Hormone / Q000134:cerebrospinal fluid* / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology*; D008253:Macaca mulatta; D008297:Male; D009034:Mother-Child Relations; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology*
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone
keywords: ACTH; cortisol; development; dexamethasone; macaque; sex difference