Title: Neuroendocrine Consequences of Dominance and Subordination
Name: Randall R. Sakai
University of Cincinnati Medical Center
Department of Psychiatry
Year: 1997
Type: Research Grant

The visible burrow system (VBS) provides a unique model for studying complex behaviors in rat social groups in a semi-naturalistic environment. In this setting, dominance is associated with the expression of species-typical aggressive behaviors. The studies in our proposal allowed us to explore the basis of these behaviors at levels not feasible or ethically permissible in human subjects. Specifically, we have assessed multiple behavioral, physiological, chemical and neurological parameters in rats before, during and after they live in the VBS and experience hierarchy formation. Our studies are designed to discover specific neurochemical and hormonal signaling pathways linked to both dominant and subordinate behaviors. Once these correlates are identified, it is our long-term goal to then develop and use experimental interventions in an attempt to modify offensive/aggressive behaviors of dominants and defensive behaviors of dominant and subordinates. In addition to novel insights into the biochemical basis of aggressive behavior, these studies should provide us with a wealth of new and important information on the physiological consequences of prolonged exposure to subordination, a stressor that is of particular relevance to humans. Because this kind of psychological stress has been associated with an increased incidence of both mental and somatic illnesses, a greater understanding of the neurochemical and endocrine correlates and consequences of stress should lead to more effective therapeutic approaches to stress-related disorders.

Our recent studies using the VBS have documented behaviors in the subordinate rats that include reduced social, sexual and aggressive activity, changes in sleep cycles, and weight loss associated with lower food intake. This spectrum of behaviors is characteristic of human symptoms of chronic subordination, loss of job and job security and clinical depression. This experimental preparation therefore provides an important and unique animal model for the analysis of the behavioral, neuroendocrine and neurochemical changes that accompany the process of becoming subordinate as well as those involved with the development of dominance.

Using a visible burrow system to investigate social interactions, we have found that subordinate status is positively correlated with plasma stress hormone levels but negatively correlated with plasma androgen levels. We have also determined that a significant subset of subordinate animals become non responsive to novel stressors. These findings are consonant with what has been reported for humans living under conditions of chronic stress situations. We have therefore begun to investigate possible neural correlates of the subordinate state, and have recently found that animals living in the visible burrow system have changes in neuron morphology. These data are important for several reasons. First, altered neuron morphology is indicative of chronically altered neuronal activity and connectivity. Second, the brain region in which we have found these changes, the hippocampus, is known to be involved in responding to and learning about emotional situations. Finally, the data are consistent with what has been reported using different models of experimental stress. Of primary interest to us is that when the data were analyzed by social status, the dominant animals were observed to have the greatest degree of neuronal remodeling, with the subordinate animals having significantly less. This key finding suggests that the reports of neuronal restructuring that has been observed in other experimental models may in fact reflect different underlying endocrine and neurochemical mechanisms. It further suggests that a more sophisticated animal model, such as the visible burrow system, will be necessary for uncovering and ultimately understanding the complex changes that occur in the brain when individuals are stressed in naturalistic ways. At this point, it is unclear if the changes observed are harmful to the animal in and of themselves, especially since it is the dominant animals that display the greatest neuronal change. Our studies continue to build upon our previous research by determining whether these social-stress-induced changes in the brain are reversible or not, and whether changes in neurogenesis or neurodegeneration may produce pathological situations to these animals.