Regulation of neuropeptide Y in the basolateral amygdala in a rodent model of conditioned fear
Neuropeptide Y (NPY) is an endogenous anxiolytic compound, decreasing stress and anxiety-like responses in several rodent models. Within the basolateral amygdala (BLA), a crucial region involved in mediating anxiety and modulating hippocampal memory processes, the anxiolytic actions of NPY are exerted via activation of NPY Y1 and Y5 receptors. Widespread distribution of NPY receptor and GABA co-localization was found within many brain regions. Specifically within the BLA, 64–85% of Y1r immunoreactive cells and 56–80% of Y5r cells were co-localized with GABA. Additionally, 73% and 40% of GABAergic cells were colocalized with the Y1 and Y5 receptors, respectively, suggestive of a strong NPY influence on GABA tone in this region. The influence of conditioned anxiety, produced using a conditioned emotional response (CER) paradigm, on NPY expression in the BLA and hippocampus was examined. Rats were conditioned to three days of footshock and then, on day four, placed in the footshock chamber without receiving a shock. These rats exhibited an increased number of defecations, increased duration of freezing and overall decrease in rearing and explorations as compared to non-shock controls (p < 0.0001). NPY fiber staining was significantly increased in the BLA of stressed rats as compared to non-stressed or home cage controls (p < 0.001). Presence of an anxiety-provoking stimulus immediately prior to sacrifice was required for the observed NPY increase, suggesting a phasic rather than a chronic up-regulation of NPY in the BLA. NPY-Y1 and Y5 receptor immunostaining in the BLA did not greatly differ between stress groups. Administration of acute (1 day) or chronic diazepam (10 days; 3mg/kg, i.p.), as well as acute or chronic paroxetine (14 days; 10mg/kg, i.p.) significantly decreased behavioral anxiety, as evidenced by increasing exploration time and decreasing freezing time compared to vehicle controls. The increase in NPY fiber density observed in the BLA of stressed rats was blocked by acute administration of diazepam only. Stress induced increase in NPY immunoreactivity in the BLA and hippocampus after CER may serve as a compensatory response to buffer the behavioral effects of anxiety-provoking stimuli. In conclusion, NPY may be crucial in providing an optimal and appropriate response to stressful stimuli by modulating neural activity of GABAergic interneurons.
0384: Behaviorial sciences