Alcoholism is a major public health problem in the United States, resulting in the annual death of tens of thousands of Americans and costing billions of dollars. The development of animal models of alcoholism will play an important role in understanding the biological factors that contribute to the development of alcoholism and provide a means of testing novel medications for its treatment. A nonhuman primate model of alcoholism has been developed at the NIAAA's Laboratory of Clinical Studies in which animals are subjected to one of three different rearing manipulations that are designed to expose them to varying degrees of early life stress. When tested years later, significant group differences in oral ethanol self-administration behavior are observed.
The first aim of the current application is to generate a detailed neuroendocrinological profile for eight monkeys in each of the three rearing groups (n=24) by measuring the dose-effect and time-course of the HPA axis response to the alpha 2 adrenergic antagonist yohimbine, the mixed serotonin agonist mCPP, the benzodiazepine receptor inverse agonist beta-carboline-3-carboxylic acid ethyl ester, and the putative CRHR1 receptor agonist EG1.
The second aim i s to quantify individual and group differences among the animals in their motivation to intravenously self-administer ethanol by examining the extent to which they persist on a progressive ratio schedule of intravenous ethanol reinforcement.
The third aim i s to determine whether there are individual and/or group differences in the effect that the pharmacological stressors administered in Experiment 1 have on progressive ratio performance for intravenous ethanol self-administration when given as pretreatments. These studies will contribute to a better understanding of the biological basis of alcoholism, which is a first step toward the development of effective pharmacotherapeutic interventions.
