We propose three highly interrelated studies that will utilize the cohorts of stressed and control nonhuman primates that were generated during our previous funding period of the Conte grant. Study 1 (investigator: Stuart Zola, Ph.D.) asks what are the effects of early stress on subsequent cognitive abilities, with a particular emphasis on declarative and nondeclarative memory functions. Behavioral tasks that are selectively sensitive to medial temporal damage, to striatal damage, and to frontal lobe damage, respectively will be used to assess the impact of early life stress on subsequent development of cognitive abilities, especially memory function. Study 2 (investigators: Lisa Parr Ph.D., Mar Sanchez, Ph.D.) asks what are the effects of early stress on the development of emotional behavior, with an emphasis on fear and anxiety, and changes in cerebral glucose metabolism. Study 3 (investigator: Leonard Howell, Ph.D.) asks whether early stress results in subsequent vulnerability to acquiring cocaine self-administration more rapidly than control monkeys, and whether early stress makes one more resistant to extinction compared to control monkeys. All of the studies will use structural and/or functional brain imaging to additionally clarify the relationship between behavioral changes and changes in brain, and will obtain neuroendocrine, HPA axis function, and other neurochemical assessments to clarify the relation between behavioral changes and brain chemistry as a consequence of early life stress. An additional advantage is that Study 1 and Study 2 will use the same groups of monkeys. This is both an efficient use of this very valuable resource, and it allows us to directly compare findings in two different domains of behavior, i.e., memory and emotion, in the very same animals. By necessity, an entirely separate group of monkeys will be used for Study 3. The findings from all of the studies proposed here using nonhuman primate animal models will have important theoretical implications as well as obvious clinical relevance and direct application to understanding the effects of early life stress on subsequent human cognitive and emotional development and function. In particular, this work will identify brain regions that are vulnerable to the effects of early stress. Moreover, the findings should illuminate important points about the organization of memory, emotion, and addictive-like behavior in the mammalian brain.
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