Molecular basis for the development of individual differences in the hypothalamic-pituitary-adrenal stress response

Abstract

1. Several years ago, investigators described the effects of infantile handling on the development of hypothalamic-pituitary-adrenal (HPA) responses to stress in the rat. Rat pups exposed to brief periods of innocuous handling early in life showed reduced HPA responses to a wide variety of stressors, and the effect persists throughout the life of the animal. These effects are robust and provide an excellent model for understanding how early environmental stimuli, which are external to the organism, alter neural differentiation and, thus, neuroendocrine responsivity to stress. 2. This paper reviews the endocrine mechanisms affected by early handling and our current understanding of the neural transduction of environmental events and their effects at the level of the target neurons (in the hippocampus and frontal cortex). 3. In brief, handling serves to increase glucocorticoid receptor gene transcription, increasing sensitivity to glucocorticoid negative feedback regulation and, thus, altering the activity within hypothalamic corticotropin-releasing factor/vasopressin neurons. Together these changes serve to determine neuroendocrine responsivity to stress.

Behavioral/Environmental Intervention Improves Learning After Cerebral Hypoxia-Ischemia in Rats

“…Previous reports and the present results are consistent with the possibility that the cognitive benefits of handling only become apparent in a brain that has experienced some neuronal loss. The duration of handling used was shorter than in most studies; Meaney et al 22 found that handling over the second week of life was somewhat less effective than handling over the entire first 3 weeks. To model behavioral intervention after a biological insult to the premature infant brain, we induced injury on P7 and restricted handling to the post-HI period (P8 to P14), a design that may have reduced the power of handling.…”

“…This is consistent with the suggestion that the effects of early handling afford the animal better feedback regulation of the hypothalamic-pituitary-adrenal response to stress. 22 There are several possible mechanisms by which our behavioral intervention might have improved placenavigation performance. We considered the possibility that early behavioral intervention after acute brain injury in neonatal rats might result in a change in lesion size.…”

Sex Differences in Hormonal Modulation of Anxiety Measured with Light-Enhanced Startle: Possible Role for Arginine Vasopressin in the Male

“…Interestingly, T has been shown to ameliorate mood in hypogonadal and aged men and in perimenopausal and elderly women. T has also been shown to reduce activation of the hypothalamic-pituitaryadrenal (HPA) axis in rats, providing yet another possible mechanism whereby T reduces indices of anxiety (Meaney et al, 1993;Viau and Meaney, 1996;Viau et al, 2001Viau et al, , 2005Viau, 2002).…”

Stress and Health: Psychological, Behavioral, and Biological Determinants

“…For example, Meaney et al (1993) showed that rats raised by nurturing mothers have increased levels of central serotonin activity compared with rats raised by less nurturing mothers. The increased serotonin activity leads to increased expression of a central glucocorticoid receptor gene.…”