Aggression, impulsive choice and serotonin in male golden hamsters
Cervantes, Martha Catalina
MetadataShow full item record
Aggression studies in laboratory animals have largely focused on natural species-specific forms of aggression that poorly reflect pathological types of aggression in humans. The primary goal of this dissertation was to identify and characterize a subtype of aggression in support for a congenital animal model of reactive/impulsive-aggression in humans. Experiments using novel second-by-second analyses to investigate for individual differences in aggression and impulsive choice showed detailed quantitative and qualitative differences, and identified a convergence of behaviors to one distinct impulsive-aggressive profile in high-attack frequency (HAF) hamsters. As aggression and impulsivity widely implicate the serotonin (5HT) system, and previous studies have similarly characterized the neural control of aggression in hamsters, it was hypothesized that impulsive-aggression in HAF individuals was associated to common neurobiology. While 5HT does play a role, immunocytochemical experiments and pharmacological manipulations showed a distinct neurobiological profile of decreased 5HT availability, increased densities of 5HT1A and 5HT3 receptor subtypes, and drastically differential and opposite phenotypic-dependent reactivity to 5HT3 receptor blockade. Moreover, the current studies also showed that while 5HT3 receptor activity has broad effects, attenuating all behavioral aspects of the impulsive-aggressive phenotype (i.e. aggression, repetitiveness, fragmentation, and impulsive choice), 5HT1A receptor activity seems to have more limited effects. Additional retrospective studies investigated developmental and etiological differences between the phenotypes. HAF adults were associated with low agonistic activity in early puberty and an early emergence of impulsivity-related characteristics. These data indicate a differential developmental trajectory of behavior and accelerated maturation, consisting of a lack of play fighting during early puberty. The HAF phenotype was additionally associated with paternal, but not maternal influence, suggesting male genetic contribution. Together, these data support a congenital animal model that better reflects reactive forms of aggression in humans through the behavioral, neurobiological, and developmental characterization of HAF hamsters described herein. These data have pre-clinical and clinical significance and can be applied to diagnostic and preventative measures, as they illustrate the importance of distinguishing predictions about extreme fringe populations from that of normal populations, point towards more specific pharmacological therapeutic applications, identify early predictive behaviors of impulsive-aggression, and suggest heritability.