2010 New Grant Project Profiles
ABMRF/The Foundation for Alcohol Research has played a major role in shaping the early careers of the most prominent alcohol researchers across North America. Since our founding in 1982, we have maximized our impact as a relatively small foundation by centering the grant program on novel research proposals put forth by the most promising investigators. Recently funded research projects which are described below offer an exciting opportunity to view the future through the studies currently underway by Foundation grantees.
Behavioral and Social Advisory Council
James Henson, Ph.D., Old Dominion University, “A daily process examination of unintended drinking among college students.”
Many institutions of higher learning continue to commit substantial resources toward the prevention of and intervention on alcohol abuse and negative consequences among college students. Unfortunately, typical alcohol intervention effects tend to be moderate and short-lived. The primary objective of this project is to investigate one potential mechanism that may explain the underwhelming effects of most college-drinking interventions. Specifically, most models of alcohol use, and thus most interventions, assume that drinking stems from conscious deliberation, and thus they focus on assessing and altering intentional behavior. However, the present study posits a model of unintentional drinking, or a Model of Unplanned Behavior. This model assumes that unintentional drinking is particularly problematic (i.e., particularly likely to lead to more negative alcohol-related consequences); therefore, interventions that focus solely on intentional drinking ignore the substantial problems associated with unintended drinking. Whereas an individual who intends to binge-drink is more likely to be prepared to do so in a relatively safe manner (e.g., plan a designated driver, drink with responsible friends), an individual who drinks beyond what one intends to drink is more likely to be unprepared to handle the consequences from drinking (e.g., driving home from a bar). Using state-of-the-art Ecological Momentary Assessment techniques via hand-held assessment devices, this research will examine if the gap between daily drinking intentions and daily drinking behavior predicts alcohol-related problems beyond typical intention-based predictors. We predict that this new Model of Unplanned Behavior may better account for alcohol-related problems, which may in turn be used to develop more effective preventions and interventions that are directly focused on harm reduction and decreasing alcohol-related problems.
Sherry Lipsky, Ph.D., University of Washington, “Trajectories of alcohol misuse and traumatic intimate partner violence: Implications for alcohol prevention and intervention.”
Alcohol misuse, such as binge drinking, and alcohol use disorders are important risk factors associated with intimate partner violence victimization. Studies of the temporal relationship between alcohol use and traumatic experiences of partner violence in particular are limited, with the majority of studies focused on traumatic experiences overall. Further, the current literature suggests that gender may differentially impact the relationship between alcohol use and partner violence. Other factors may affect this relationship, such as childhood traumatic experiences. Although childhood trauma, mainly family violence and dysfunction, has been associated with alcohol misuse and with partner violence, the role of childhood trauma in the alcohol-partner violence relationship has not been well-studied. In addition, much less is known about how race/ethnicity might affect these complex relationships. This study will analyze two waves of a national household survey, The National Epidemiologic Surveys on Alcohol and Related Conditions. The surveys, conducted in 2000-2001 and 2004-2005, included the U.S. non-institutionalized population 18 years of age and older. The main goal of this study is to examine whether alcohol misuse or alcohol use disorders lead to adult traumatic partner violence experiences or if those experiences lead to alcohol misuse and alcohol use disorders. This study will also examine the effect of childhood trauma and race/ethnicity on these relationships among the three major racial/ethnic groups in the U.S., non-Hispanic Whites, Blacks/African Americans, and Hispanics/Latinos. These questions are of major public health importance given the substantial occurrence of partner violence and alcohol problems in the U.S. and the devastating effects they can have on the lives of individuals and families. Increasing our understanding of alcohol misuse in the milieu of violence and trauma, and identifying potential gender and racial/ethnic-specific factors related to these experiences, will help to inform the development of early and targeted prevention and intervention efforts.
Tara White, Ph.D., Brown University, “Imaging biphasic alcohol effects in heavy drinkers.”
Dr. White’s ABMRF project investigates the impact of alcohol on brain processing over the time course of its effects. When consumed at moderate to high doses, alcohol has a unique, time-delimited impact on mood. Approximately 10-30 minutes after consumption people report that alcohol improves mood, making them feel “up”, positive and activated. This effect lasts a short time, and is then be followed by a quieter, more negative, “descending phase”, in which people report feeling tired, negative, or sluggish, particularly if the original dose of alcohol was moderate to high and if no additional alcohol has been consumed. Differences in the degree to which people experience either the positive or the negative effects of alcohol could pose either a vulnerability to, or a resilience from, alcohol misuse, particularly in heavy drinkers who may be uniquely at-risk for both responses. There are also significant gaps in our knowledge base related to the negative phase, which has not yet been well studied using brain imaging techniques – such as fMRI -- in humans. The present study begins to fill these gaps, investigating the acute effects of consumed alcohol on fMRI brain responses during 3 separate points in time in each heavy drinker studied – during the positive phase, during the negative phase, and during a non-alcohol control period. The present ABMRF project thus permits “within-subject” collection of fMRI data in healthy volunteers who are heavy drinkers, who are not yet dependent on alcohol but who are at risk for alcohol misuse because of their personal drinking histories. The results of the project will provide proof-of-concept data for a new program of alcohol research using fMRI. The project is important because it increases our understanding of the brain mechanisms through which chronic alcohol use may affect functional brain responses after consumption of alcohol, using a moderate alcohol dose (0.6) that is routinely consumed by heavy drinkers in the real-world.
Medical Advisory Council
Cedrick Dotson, Ph.D, University of Florida College of Medicine, “Hormonal modulation of alcohol taste.”
Excessive consumption of alcohol affects grave social, psychological, and physiological problems within human societies. A substantial body of evidence from human and animal studies has supported the existence of a relationship between the ingestion of alcohol and the consumption of sweet substances. Collectively, these findings suggest that sweet taste perception plays a significant role in alcohol consumption. Findings from our laboratory, as well as those from other researchers, have shown that various hormonal signaling systems (e.g., glucagon-like peptide-1 (GLP-1), glucagon and leptin), which contribute to the bodies ability to maintain stable glucose levels, and/or, through actions in various places throughout the body (e.g., brain, stomach), promote the state of feeling full or “sated,” can each act to modulate sweet taste function through actions on taste buds in the tongue. However, whether or not these hormones can modulate the taste of alcohol, and its subsequent consumption, remains unclear. We intend to determine if these hormones play a significant role in modulating the taste of alcohol. The proposed studies will address the interaction between these hormones and the taste receptors in the tongue that convey “taste” information to the brain. Understanding the relationship between taste function, hormonal regulation and alcohol consumption will facilitate the development of new therapeutic targets that can help address the problem of alcohol over-consumption in society. Indeed, an understanding of the factors that can influence or modulate alcohol ingestion is crucial to finding the most effective ways to prevent and treat alcohol misuse and alcoholism.
Isabel Quadros, Ph.D., Tufts University, “Alcohol-heightened aggression in mice: modulation by CRF-serotonin interactions in the dorsal raphe nucleus.”
Violence and aggression are among the most harmful and damaging consequences associated with alcohol drinking. Epidemiological data show that more than 50% of violent crimes are linked to alcohol. Under certain conditions some individuals present aggression-heightening effects after consuming alcohol, an observation that is consistent across humans, non-human primates and rodents. The present proposal will increase our understanding of the neurobiological mechanisms through which alcohol escalates aggressive behavior. The focus is the modulation of serotonin function by Corticotropin-Releasing Factor (CRF) as a critical neurobiological mechanism in the transition to escalated aggression under the influence of alcohol. We propose that the dysregulation of CRF-serotonin interactions, particularly in the dorsal raphé nucleus, may characterize the emergence of escalated aggressive behavior after alcohol consumption in rodents. Preliminary results show that blockade of CRF1 receptors in the dorsal raphé nucleus selectively attenuates alcohol-heightened aggression in mice, while blocking CRF2 receptors in the dorsal raphé further escalates aggressive behavior. We hypothesize that the apparent contrasting roles of CRF1 and CRF2 receptors on alcohol-related aggression reflect differential modulation of serotonin function in the dorsal raphé. Specifically, experiments in mice are designed to: 1) Characterize the role of CRF and its receptors in alcohol-heightened aggression. 2) Determine if the dorsal raphé nucleus is a critical site for CRF effects on alcohol-heightened aggression. 3) Investigate the extent to which CRF modulation of serotonergic projections to the prefrontal cortex is a critical determinant of escalated aggressive behavior promoted by alcohol. The proposal will increase the knowledge on mechanisms that promote alcohol-heightened aggression, and further identify targets for therapeutic interventions.
Jun Wang, M.D., Ph.D., Ernest Gallo Clinic and Research Center, “Ethanol-mediated facilitation of dorsostriatal NMDAR activity and alcohol drinking behavior.”
Addiction is a maladaptive form of learning and memory. I recently observed that excessive alcohol consumption in rodents causes a sustained increase in the activity of the NMDA receptor (NMDAR), an important channel controlling learning and memory processes, in a part of brain called the dorsal striatum. Additional behavioral findings suggest that this increase may contribute to the development and maintanance of alcohol-drinking behaviors. In this proposal I aim to identify the mechanism by which the long-lasting activation of the NMDAR induces maladaptive memory processes that ultimately results in the development and maintancence of alcohol-drinking behaviors. The cellular model of learning and memory is long-term potentiation (LTP) of another ion channel called the AMPA receptor (AMPAR)-mediated synaptic transmission, a process whereby neural information transfers from one nerve cell to another. The induction of LTP of AMPAR-mediated synaptic transmission in striatal nerve cells requires the activation of NMDARs. I, therefore, plan to investigate whether facilitated NMDAR activity in the dorsal striatum, induced by repeated exposure of rodents to alcohol, leads to potentiated AMPAR activity. In addition, nerve cells in the dorsal striatum alternate between two resting-voltage states: the DOWN-state and the UP-state. Striatal nerve cells excite only during the UP-state allowing information flow through the striatum in the brain network. Importantly, NMDAR activity controls resting-voltage during the UP-state, thereby directly governing the excitability of striatal nerve cells. I will, therefore, examine whether repeated exposure of rodents to alcohol increases the amplitude of UP-state voltages in the dorsal striatum. I predict that through one or both of these mechanisms, repeated exposure of the brain to alcohol will abnormally strengthen striatal-dependent learning, thereby enhancing alcohol-seeking and consumption. Results generated from this proposal will greatly expand our knowledge of the mechanisms that contribute to the development and maintanance of alcohol-drinking behaviors.
Please refer to the links below for grants awarded in previous years: