The Effects of Corticotropin-Releasing Factor and Restraint Stress on Prepulse Inhibition of the Acoustic Startle Response in Rats

Stress can be broadly defined as “an actual or anticipated disruption of homeostasis or an anticipated threat to well-being” (Ulrich-Lai and Herman 2009). When a person develops maladaptive stress responses or coping strategies, the effects of stress can become deleterious and pathological conditions can arise, including psychiatric disorders. For example, exposure to stressful events can exacerbate symptoms in people suffering from schizophrenia or can trigger the onset of anxiety disorders such as post-traumatic stress disorder (PTSD). Due to the complex neurobiology of schizophrenia and PTSD, we focused our research on one particular aspect, or endophenotype, known to be aberrant in these disorders. Decreased prepulse inhibition (PPI) of the acoustic startle response is the endophenotype that we used to investigate processes that contribute to stress-related psychiatric disorders. PPI is the reduction in startle amplitude caused by brief presentation of a non-startling acoustic stimulus shortly prior to a startling stimulus, and is recognized as a simple operational measure of sensorimotor gating. Since PPI can be assessed in both humans and rodents using nearly identical parameters, it a useful tool for investigating human information processing deficits using animal models. ^ We proposed that corticotropin-releasing factor (CRF) contributes to the reduced PPI observed in people diagnosed with stress-related psychiatric disorders. Considerable evidence supports this hypothesis. First, CRF is one of the most important neurotransmitters involved in behavioral components of the stress response. Second, central infusion of CRF decreases PPI in rodents. Third, CRF acts via CRF receptors located in regions of the brain that modulate PPI. Fourth, the brain regions that modulate PPI and express CRF receptors are known to be abnormal in schizophrenia and PTSD. ^ Although central infusion of CRF decreases PPI in rodents, it is not known whether CRF decreases PPI indirectly via its effects on other neurotransmitters, such as serotonin, or whether stress modulates PPI via the endogenous CRF system in the same manner that exogenous CRF modulates PPI. As a result, the ultimate goal of this dissertation is to explore these topics and to further our understanding of the mechanisms by which CRF and stress affect sensorimotor gating.