SOCIAL NEUROSCIENCE—APPLICATIONS TO ADDICTION
Social Defeat, Gene Expression, and Vulnerability to Addiction
Huda Akil, Ph.D.
[Slides not available]
In humans, it is well established that stressful life events play an important role in triggering drug-seeking behavior in vulnerable individuals and in contributing to the maintenance and relapse of substance abuse. Because life events are typically psychosocial in nature, it is important to ask in animal models whether there are distinct neural mechanisms that encode social stress and how these mechanisms affect drug-seeking behavior.
We have chosen territorial social behavior in male rodents as our animal model. This behavior typically results in a clearly dominant and clearly subordinate animal, and the latter is presumed to have undergone “social defeat.” We characterized the neural pathways that encode agonistic behavior and distinguished the subordinate from the dominant animal. The pathways associated with social defeat show remarkable parallels to the circuitry implicated in severe depression in humans.
We then used social defeat in animals that have different environmental reactivity, different propensities to seek novelty, and different endocrine responses to stress and, importantly, that exhibit a differential propensity to self-administer drugs of abuse. This is the high-responder versus low-responder trait. We have shown that social defeat stress has a differential impact on the behavior of these two types of animals. Moreover, the neural changes associated with social defeat are unique in these two behavioral phenotypes. Many of the observed changes are relevant to the mechanisms of neuroplasticity that appear to differ between animals and are critical for responsiveness both to social defeat stress and to the development of addiction.
The findings will be discussed in terms of multiple pathways to addiction and their distinctive impact on brain and behavior.
PET Imaging of Dopamine D2 Receptors in Cocaine Abuse:
A Social Neuroscience Perspective
Michael A. Nader, Ph.D.
The primary goal of this research is to achieve a better understanding of the individual differences in the susceptibility and vulnerability to the reinforcing effects of cocaine using a unique nonhuman primate model of drug abuse. To accomplish this, we have combined the study of primate social behavior with intravenous drug self-administration and the noninvasive brain imaging procedure positron emission tomography (PET) to examine how environmental and pharmacological variables influence the behavioral and reinforcing effects of cocaine. These studies use male and female monkeys to examine trait variables that are predictive of eventual social rank, such as locomotor activity, measures of impulsivity, hormone levels, and measures of dopamine (DA) and serotonin function with PET. We also examine how social group formation influences these measures and how cocaine self-administration is affected by social rank. Studies will be described related to the plasticity of the DA system during cocaine abstinence and following social group reorganization as well as to the impact of these manipulations on cocaine intake. The use of these novel and homologous nonhuman primate models of cocaine abuse should aid in understanding how environmental and pharmacological variables contribute to the vulnerability, maintenance, and relapse to drugs of abuse. This information could lead to better treatment and prevention strategies.
Getting To Know You: Reputation and Trust in a Two-Person Economic Exchange
P. Read Montague, Ph.D.
Recent work in neuroimaging has combined computational models with novel imaging methods to begin to probe the neural correlates of social exchange. The importance of these approaches to understanding reward-processing and the nature of addictive (pathological) reward-processing derives in part from the influence of group pressures on perception and action. In the context of a group, perceptions can be dramatically changed, and valuation and decision-making can be perturbed. The growing capacity to make multibrain measurements in the context of live social exchanges offers a new approach to the dynamic brain states that underlie both the normal and pathological processing of social signals and the decisions they engender. In this talk, I will emphasize the need to use quantitative behavioral models to help guide the design and interpretation of social exchange experiments.
Social Cognitive Neuroscience: Exploring the Psychological and Neural Bases of Socioemotional Experience and Behavior
Kevin Ochsner, Ph.D.
The past few years have seen an explosion of interest in using cognitive neuroscience methods to study the mechanisms underlying human emotion and social behavior. In this talk I will give a brief overview of the social cognitive neuroscience approach that motivates this work; illustrate its usefulness for studying emotion regulation, using examples from our own research on cognitive reappraisal; and consider the relevance of this work for understanding the mechanisms underlying substance abuse.