Interactions of early rearing and later environment on brain self-repair and compensation

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The area that this research is most clearly relevant to is that of developmental psychopathology in humans. The questions are: "Why doesn't the central nervous system and behavior recover from early social environmental privation after the individual is introduced to an optimal and even therapeutic environment in many cases? Why do drug treatments help ameliorate the symptoms of psychopathology, but rarely effect a cure." The focus of the proposed studies is an outgrowth and continuation of studies in non-human primates. The overall aim of this project is to identify the circumstances and then the neurobiological mechanisms by which experiences later in life can substantially reverse the adverse behavioral effects of privation of maternal care in the rat. That is, "self-repair" - the mechanisms by which the central nervous system (CNS) and the organism as a whole recovers from early deprivation, and the environmental factors that can promote or limit this process. The proposed project invloves the study of rat pups reared either by their mothers or in conditions comparable to a human neonatal intensive care unit, and then in standard laboratory or socially complex environments. Changes in the brain related to behavior will be investigated at the neuroanatomical and cellular level. An important goal is to understand how therapeutic drugs might interact with environmental factors that cause changes in brain mechanisms. The overall objective is to discover why self repair is often uncertain or incomplete, and then how to promote this process.