GABAA positive modulators, corticosterone, and schedule-heightened aggression in mice

Aggressive confrontations can be reinforcing and even pleasurable to certain individuals. However, little is known about the neurobiology underlying the seemingly positive consequences of aggression. This thesis describes an experimental procedure designed to assess how the opportunity for aggression reinforces the behavior of mice. One objective was to investigate how GABA _A receptor positive allosteric modulators can affect both responding for aggressive behavior and aggressive behavior itself. A second objective was to examine to which extent the actions of the adrenal steroid corticosterone are required for aggression-reinforced behavior. The third objective was to determine whether corticosterone interacts with GABA_A receptor positive modulators to regulate heightened aggression. Data suggest that neurosteroid modulation of the GABA_A receptor can influence the performance of aggression and sucrose intake as well as responses that may reflect the motivation to engage in these behaviors. In contrast, positive modulation by benzodiazepines may be more important to regulate the motivation to fight or drink sucrose. This experiment suggested that performing the FI10 to be reinforced by aggression initiates a neurochemical process that heightens aggressive behavior and attenuates the aggression-heightening effects of GABA _A positive modulators. Part III. The HPA axis is one of the systems engaged as a mouse works a schedule of reinforcement. As the mice performed the FI10 to be reinforced by aggression or sucrose, their plasma corticosterone levels nearly tripled by the time of reinforcement and remained elevated for at least 30 minutes. A brief, but intense fight further amplified the already high corticosterone response. Although previous results suggest that corticosterone decreases aggressive behavior, inhibition of corticosterone synthesis by metyrapone (30–100 mg/kg) reduced both conditioned nose-poking as well as the aggressive behavior following the FI. Moreover, inhibition of corticosterone synthesis facilitated the aggression heightening effects of midazolam (0.3mg/kg) and allopregnanolone (17mg/kg). These data suggest that corticosterone is required for FI performance and heightened aggression but that corticosterone also acts as a brake to prevent GABA_A positive modulators from further heightening aggression. Conclusions. Aggressive behavior can serve as a reinforcer in mice and the interactions between GABA_A receptor positive modulators and corticosterone mediate its reinforcing effect. These compounds further interact to heighten the performance of aggressive behavior. The interactions on aggressive behavior suggest that while corticosterone heightens aggression, it can also prevent further escalations. (Abstract shortened by UMI.)...