[Abstract Title]. - Society for Neuroscience

Topic: C.15.k. Anxiety disorders
Title: Neuropeptide Y (NPY) and posttraumatic stress disorder (PTSD): studies in a rodent
model of chronic variable stress
Authors: *J. L. MCGUIRE 1 , J. P. HERMAN 2 , F. R. SALLEE 3 , R. SAH 3 ;
1 Psychiatry, Univ. Cincinnati, Cincinnati, OH; 2 Neurosci., 3 Psychiatry, Univ. of Cincinnati,
Cincinnati, OH
Abstract: The development of PTSD has been associated with abnormalities in the major stress
response systems of the body, the hypothalamic-pituitary-adrenal (HPA) axis, the CNS
noradrenergic system, and the sympathetic nervous system. Pathological anxiety in PTSD is
indicative of impairment in anxiety regulating mechanisms in the CNS. A major transmitter that
is linked to the regulation of stress and anxiety is neuropeptide Y (NPY), which is increasingly
suspected to be a potential “stress resilience factor”. Currently, pathophysiological relevance of
NPY in PTSD is not known. The objective of this study was to a) develop a chronic variable
stress (CVS)-recovery model that elicits “PTSD-like” behavior and b) investigate whether NPY
expression is dysregulated in the CVS-recovery model. Adult male Long Evans rats were
subjected to variable stressors for 7 days followed by 7 d recovery period. Animals were tested
for PTSD-pertinent behavior (contextual fear conditioning, extinction and re-activation), and
NPY mRNA and protein expression. Rats exposed to CVS showed significant potentiation of
freezing response following fear-reactivation (p=.0247, t=2.540, df=13), as well as delayed
impairment of fear extinction (p=.008, t=3.177, df=12). NPY expression was attenuated in the
hippocampus after 16 hours (35.29% below controls, p=.0251, t-2.632, df=10) and amygdala
after 7 days (38.4% below controls, p=.045, t=2.258, df=10). These are regions relevant to
contextual fear-conditioning. Our studies indicate that persistent NPY dysregulation in limbic
regions of CVS animals may contribute to enhanced fear responses upon re-exposure as well as
impaired extinction. NPY may be relevant to the pathophysiology of PTSD.
Disclosures: J.L. McGuire , None; J.P. Herman, None; F.R. Sallee, None; R. Sah, None.
Poster
256. Anxiety Disorders: Human Biomarkers
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 256.12/Z15
Topic: C.15.k. Anxiety disorders
Support: NIMH Division of Intramural Research Program