Human alcohol research and clinical practice demonstrate that, without question, individual variation in risk for excessive drinking, in sensitivity to alcohol effects, and in response to treatment strategies are critical. Our model of ethanol self-administration in cynomolgus monkeys provides a unique and important model of alcohol abuse. Because macaque monkeys are so similar to human beings in their complex physiology, endocrinology, neurobiology and genetic code they can play a pivotal role in testing hypotheses generated from behavioral models that employ other species, particularly rodents. Further, the non-human primate can then be a key step in translating candidate mechanisms of ethanors effects into the human realm throughthe use of imaging techniques, functional genomics and behavioral outcomes. Finally, macaques can be effectively used to target mechanistic hypotheses generated by studies in humans. Thus, our primary focus of the next funding cycle for the Center for the Neurobehavioral Study of Alcohol (CNSA) is to concentrate efforts on characterizing antecedent and consequent factors related to excessive ethanol self-administration in this monkey model. To complement the non-human model of self-administration, we will also study a second animal model. Rats will be maintained under a scheduled-induced polydipsia procedure that produces excessive alcohol self-administration as evidenced by physical dependence upon withdrawal. We will use this procedure to investigate additional and complimentary mechanisms of neurobiologicaladaptations in response to chronic ethanol self-administration. Taken together, the CNSA will focus efforts on understanding antecedent behavioral and physiological variables as well as consequent molecular, cellular, neuroanatomical, physiological and behavioral effects of excessive self-administration of ethanol in understanding two established models of alcohol self-administration.
Specific Aim 1 : To provide CNSA Investigators with adult cynomolgus monkeys (Macaca fascicularis) that have undergone the following standardized ethanol self-administration procedure.
Specific Aim 2 : To provide CNSA Investigators with adult rats (Long Evans) that have been subjected to a standardized schedule-induced polydipsia procedure resulting in physical dependence upon ethanol.
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