Publication Date


Document Type


Committee Members

Dragana Claflin (Committee Member), David Cool (Committee Member), Michael Hennessy (Advisor), James Lucot (Committee Member), Patricia Schiml-webb (Committee Member)

Degree Name

Doctor of Philosophy (PhD)


Separation from the maternal attachment figure, particularly when it occurs in a novel or threatening environment, reliably increases pituitary-adrenal activity in a number of species, and is thought to increase later susceptibility to psychopathology in humans. However, little is known about the central mechanisms mediating these effects. Therefore, I investigated cortisol and ACTH levels in plasma, corticotropin-releasing factor (CRF) mRNA expression in the hypothalamic paraventricular nucleus (PVN), and c-Fos activity in a circuit [medial amygdala (MeA)- bed nucleus of the stria terminalus (BNST)] thought to drive pituitary-adrenal activity during exposure to psychological stressors, as well as in the PVN. Measurements were taken in 16 (+/-1)-day-old infant guinea pigs (Cavia porcellus) during maternal separation, exposure to a novel environment, and exposure to both separation and a novel environment. Levels of plasma cortisol and ACTH, and PVN CRF mRNA expression were elevated only when animals were exposed to both separation and novelty. The putative MeA-BNST circuit was activated during exposure to novelty regardless of whether or not the animals were separated, and c-Fos activity in the PVN was elevated during separation regardless of whether infants were in a novel environment. In sum, there were effects due only to separation; others due only to novelty; and some due to both. These results suggest that CRF activity in the PVN can account for changes in pituitary-adrenal activity during separation in a novel environment. Further, it appears that the effect of novelty on the hypothalamus is mediated at least in part by a circuit from MeA to BNST to PVN. However, other factors appear to mediate activation of the PVN during separation from the attachment figure in a familiar environment, and the lack of activation in the PVN when the attachment figure is present in a novel environment.

Page Count


Department or Program

Biomedical Sciences

Year Degree Awarded