September 22, 1997

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The more newborn rat pups are licked and groomed by their mothers, the better equipped they are to handle acute stress in adulthood, report Emory University's Paul M. Plotsky, Ph.D., and his McGill University colleagues in this week's issue of Science.

Dr. Plotsky is applying the current findings and those of his earlier work to observational human studies of maternal support (or lack thereof) of infants born prematurely or born to mothers diagnosed with significant postpartum depression.

Those rats in the current investigation who received the most infantile stimulation handled stress well both externally -- by exhibiting appropriate behaviors -- and internally -- as evidenced by an appropriate and balanced response by the animal's endocrine system.

Researchers have long suspected that early experiences affect the long-term development of a complex aspect of the central nervous system (CNS) known as the hypothalamic-pituitary-adrenal (HPA) response. The basis for this hypothesis can be attributed in great part to earlier work that showed "handling" improved behavioral and endrocrine stress responses. Handling involves separating, as a group, a litter of rat pups from their mother for a few minutes each day for the first 10 days after birth. The action is seen not as maternal deprivation, since mother rats routinely leave the nest for varying periods of time after birth, but as a form of infantile stimulation.

The current study shows a high correlation in "handled" rat pups between optimum maternal care -- as measured by amount of licking and grooming, and an arched back form of nursing -- and better stress responses in later life.

"These findings provide support for the Levine hypothesis that the effect of postnatal handling on HPA development is mediated by effects on mother-pup interaction," the authors report. "Thus handling increases the frequency of licking/grooming and these maternal behaviors are, in turn, associated with dampened HPA responsivity to stress."

Several physiologic measurements noted by the McGill-Emory team verified the association in adult rats between the desirable trait of HPA inhibition and maternal care. Specifically, pituitary adrenocorticotropic hormone (ACTH) and corticosterone response to acute stress were reduced, levels of hypothalamic corticotropin-releasing hormone (CRH) messenger RNA were reduced, and glucocorticoid feedback sensitivity was enhanced.

"We believe that the effects of early environment on the development of HPA responses to stress reflect a naturally-occurring plasticity (adaptability) whereby factors such as maternal care are able to program rudimentary, biological responses to threatening stimuli," the authors say. "Like humans, the Norway rats inhabits a tremendous variety of ecological niches, each with varied sets of environmental demands. Such plasticity could allow animals to adapt defensive systems to the unique demands of the environment. Since most mammals usually spend their adult life in an environment that is either the same or quite similar to that in which they were born, developmental 'programming' of CNS (central nervous system) responses to stress in early life is likely to be of adaptive value to the adult..."

Long range goals of this line of research are to develop interventions for human infants in whom the HPA response to stress is at risk of being compromised -- and to design drugs for adults in whom the stress response has been adversely affected and who are thus at risk for affective disorders such as addiction, anxiety disorders and depression, says Dr. Plotsky, who is professor of Psychiatry and Behavioral Sciences and directs the department's Stress Neurobiology Laboratory at the Emory University School of Medicine.

Authors of the current paper, listed in order, include: Dong Liu (first author), Josie Diorio, Beth Tannenbaum, Christian Caldji, Darlene Francis, Alison Freedman, Shakti Sharma, Deborah Pearson, Paul M. Plotsky and Michael J. Meaney; with the exception of Dr. Plotsky, all are from the Developmental Neuroendocrinology Laboratory, Douglas Hospital Research Center, Departments of Psychiatry, and Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Canada.

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Copyright ©Emory University, 1997. All Rights Reserved.
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