[Abstract Title]. - Society for Neuroscience

Poster
283. Stress-Regulated Pathways II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 283.23/PP19
Topic: E.06.f. Stress modulated pathways
Support: MH065702
Title: Reduced somatostatin neurotransmission in the basolateral amygdala may be one
mechanism by which “CRF-priming” induces persistent increases in anxiety-like behavior in the
rat
Authors: *A. MOLOSH 1 , W. TRUITT 1,2 , P. KELLEY 1 , A. DIETRICH 1 , S. FITZ 1 , G.
OXFORD 3 , A. SHEKHAR 1,3 ;
1 Dept Psychiatry, 2 Dept. Anat. and Cell Biol., 3 Stark Neurosciences Res. Inst., IU Sch. of Med.,
Indianapolis, IN
Abstract: Our previous studies have shown that repeated activation of corticotrophin releasing
factor (CRF) receptors ("CRF/Ucn1 priming") in the basolateral amygdala (BLA) results in a
behavioral syndrome characterized by persistent anxiety and panic-like responses. While this
phenomenon has been described in detail the underlying mechanisms remain elusive. To address
this question we first investigated the effects of priming on mRNA levels of receptors and
enzyme proteins from the BLA. Rats were primed, by administering small doses of the CRF
receptor agonist urocortin 1 (Ucn1, 6 fmol/100nl) or vehicle directly into the BLA once a day for
5 days. As has been observed previously, rats primed with Ucn1, but not vehicle, had significant
reductions in social interaction (SI) time, a correlate for increased anxiety-like behaviors, which
persisted for at least 3 days following the last injections. Five days after the last injection rats
were sacrificed and the mRNA levels in the BLA of vehicle and Ucn1 primed rats were
determined using RT-Profiler PCR-arrays for neuroscience (SuperArray). Of the 79 genes
screened, the mRNAs for somatostatin 2 and 4 receptors (sst2, sst4) and muscarinic cholinergic
receptor 4 were the only genes that were significantly different between treatment groups. Since
somatostatin/sst2 has been linked to anxiety-like behavior, we further studied the effect of
somatostatin (1 κM) on the properties of the BLA projection neurons utilizing the whole-cell
path-clamp of the naïve and Ucn1-primed rats. Bath application of somatostatin (3min) induced a
transient outward. Also, perfusion with somatostatin caused a significant decrease in amplitude
and frequency of spontaneous EPSC, as well as on spontaneous IPSC of the BLA projection
neurons of naïve rats. Further experiments using paired-pulse stimulation revealed that
somatostatin also induced a significant decrease of the amplitude of evoked IPSC and had no
effect on the amplitude of evoked EPSC. Taken together, our data suggests that somatostatin