Early stress & alcoholism: Neurobiological analysis

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DESCRIPTION (provided by applicant): Alcohol abuse and alcoholism are major burdens for our society. While the development of alcoholism is influenced by many factors, stress is believed to be one important etiological element. Indeed, chronic stress has been shown to alter neurotransmission in many brain systems and alter the rewarding properties of a variety of abused drugs, including alcohol. Moreover, stress during childhood contributes to an array of poor outcomes later in life including depression, anxiety disorders, and substance abuse. Little is known about the neurobiolgoical basis of the response to stress and how that might alter the way a subject responds to alcohol. Strikingly, many of the brain regions, including the orbital and medial prefrontal cortex, the amygdala and the hippocampus, that have been shown to modulate the response to stress, are also part of the brain reward circuitry, which modifies the response to drugs. This commonality of neural circuitry suggests that these regions may play a role in mediating the effects of stress on alcohol consumption. In addition, serotonin, which innervates all of the areas listed above, along with the hypothalamus, is a key neurotransmitter in the stress response, and plays a role in modifying the response to drugs as well. One model of chronic stress is produced when infant monkeys are separated from their mothers at birth and reared in a nursery. Nursery reared monkeys show an array of cognitive, behavioral, and physiological differences from normal monkeys, including dysregulation of their brain serotonin systems and a propensity to drink excessively when exposed to alcohol. Thus, the goals of this project are to: 1) study the differences in the densities of the serotonin transporter, serotonin receptors, and in serotonin gene between nursery-reared and mother-reared monkeys; 2) to characterize the drinking behaviors of these two groups of monkeys in fixed-dose and ad lib drinking environments; and to examine the changes in the serotonin system in fixed-dose vs. ad lib drinking environments.