Who Is at Risk? Population Characterization of Alcohol Self­ Administration in Nonhuman Primates Helps Identify Pathways to Dependence How Adaptation of the Brain to Alcohol Leads to Dependence: a Pharmacological Perspective from Actions to Habits: Neuroadaptations Leading to Dependence Magnetic Res

A lcohol abuse and dependence are uniquely human disorders. However, scientists sometimes use ani­ mal models to study different aspects of alcohol abuse and dependence, including aspects that cannot be easily or ethically studied in humans. For example, stud­ ies of nonhuman primates, who share many genetic, anatomical, physiologi­ cal, and behavioral characteristics with humans, can help to uncover risk factors that may either predispose a person to alcoholism or accelerate the course of alcohol addiction; these models there­ fore can shed light on these processes in humans in a way that other animal models cannot. In this article, Dr. Ferguson present findings of studies ana­ lyzing drinking behaviors in populations of nonhuman primates and the neuro­ logical factors that may underlie differ­ ences in alcohol intake levels. The authors also discuss how these findings can help scientists to prevent and treat alcoholism in humans. (pp. 289–297) THE MOLECULAR BASIS OF TOLERANCE T olerance is the body's diminished response to alcohol or other drugs over the course of time and repeated exposure. This article by Drs. Andrzej Z. Pietrzykowski and Steven N. Treistman discusses the various degrees of tolerance—acute, rapid, or chronic— and how changes in tolerance induced by alcohol may affect several processes at the molecular, cellular, or behavioral level that are related to the onset of acute, rapid, or chronic tolerance. (pp. A lcohol causes both short­ and long­ term changes in brain chemistry. Long­term changes in some of the brain's signaling systems have been linked to the behavioral effects of alco­ holism. If a heavy drinker stops drink­ ing suddenly, these changes can lead to the syndrome of alcohol withdrawal; additionally, they can make an alcohol­ dependent person who has stopped drinking more likely to relapse. As described by Drs. brain chemicals are affected by both chronic exposure to alcohol and sudden cessation of alcohol consumption. Both alcohol­induced and withdrawal­ induced changes to these signaling sys­ tems may lead to behavioral effects such as reinforcement, enhanced anxiety, and increased sensitivity to stress. The authors also explain how certain brain chemicals can be targeted by drugs meant to treat alcohol dependence. (pp. O verlapping cerebral networks asso­ ciated with behavioral control pro­ cesses such as reward­guided Pavlovian conditional responses, goal­directed instrumental actions, and stimulus­ driven habits can be altered by alcohol and other drug abuse and therefore are important to the study of substance abuse. In this article, …


THE MOLECULAR BASIS OF TOLERANCE
T olerance is the body's diminished response to alcohol or other drugs over the course of time and repeated exposure. This article by Drs. Andrzej Z. Pietrzykowski and Steven N. Treistman discusses the various degrees of tolerance-acute, rapid, or chronicand how changes in tolerance induced by alcohol may affect several processes at the molecular, cellular, or behavioral level that are related to the onset of acute, rapid, or chronic tolerance. (pp. 298-309)

HOW ADAPTATION OF THE BRAIN TO ALCOHOL LEADS TO DEPENDENCE: A PHARMACOLOGICAL PERSPECTIVE
A lcohol causes both short and long term changes in brain chemistry. Longterm changes in some of the brain's signaling systems have been linked to the behavioral effects of alco holism. If a heavy drinker stops drink ing suddenly, these changes can lead to the syndrome of alcohol withdrawal; additionally, they can make an alcohol dependent person who has stopped drinking more likely to relapse. As described by Drs. Peter Clapp, Sanjiv V. Bhave, and Paula L. Hoffman, many brain chemicals are affected by both chronic exposure to alcohol and sudden cessation of alcohol consumption. Both alcoholinduced and withdrawal induced changes to these signaling sys tems may lead to behavioral effects such as reinforcement, enhanced anxiety, and increased sensitivity to stress. The authors also explain how certain brain chemicals can be targeted by drugs meant to treat alcohol dependence.

ALCOHOL DEPENDENCE, WITHDRAWAL, AND RELAPSE
A lcohol dependence is associated with the development of physical and psychological withdrawal symptoms when alcohol use is stopped or signifi cantly reduced. According to Dr. Howard C. Becker, fear of these with drawal symptoms can perpetuate alcohol abuse in many alcoholdependent peo ple; moreover, the presence of such symptoms can trigger relapse in those who have abstained from alcohol. As Dr. Becker reports, both clinical studies and basic research studies using animal and human models have demonstrated that alcoholrelated (conditioned) cues and contexts as well as stressful stimuli and events can trigger relapse. Improved understanding of the processes con tributing to withdrawal and relapse may aid in the development of medications to treat alcohol dependence more effec tively. (pp. 348-361) MRI, is a safe and noninvasive technology that allows scientists to examine the brain's structure and func tion in real time. MRI technologies can show how the brain changes when exposed to alcohol over the short and long term, as well as how long these changes persist after a person has stopped drinking. In this article Ms. Margaret J. Rosenbloom and Dr. Adolf Pfefferbaum discuss how MRI studies, including longitudinal studies of animal models of alcoholism, can help researchers to understand how alco holism develops and how it affects the brain. Through these studies, scientists have been able to explore specific alcohol related changes to the brain, their dura tion, their effects on behavior, and the mechanisms through which the brain compensates for these changes. These studies suggest that some changes are reversed with abstinence, while others endure long after a person has stopped drinking. (pp. 362-376)

ALCOHOLRELATED NEURODEGENERATION AND RECOVERY: MECHANISMS FROM ANIMAL MODELS
A nimal studies have established that alcohol can cause damage to brain cells, resulting in the loss of structure and function as well as inhibiting the production of neurons (i.e., neurogen esis), which ultimately leads to cognitive impairment. This article by Dr. Fulton T. Crews describes models of binge alco hol consumption in rats that induce changes in cognition similar to those found in human alcoholics. Findings from these animal studies provide insight into when, where, and how alco hol abuse and abstinence recovery dynamically change braincell composi tion, which could lead to new potential therapies for neurodegeneration, men tal diseases, and alcohol use disorders. (pp. 377-388)

THE ROLE OF SELECTED FACTORS IN THE DEVELOPMENT AND CONSEQUENCES OF ALCOHOL DEPENDENCE
S tudying the risk for developing alcoholism and the negative conse quences of alcohol dependence is a complex process that requires an under standing of the various factors that may determine the degree of that risk. In this article, Rebecca Gilbertson, Robert Prather, and Dr. Sara Jo Nixon examine how gender, family history, comorbid psychiatric and substance use disorders, and age interact to influence an indi vidual's risk for alcoholism as well as how they interact with alcoholism to influence neurocognitive functioning following detoxification. (pp. 389-399)