[Abstract Title]. - Society for Neuroscience

MH 38273
HD 05751
Title: Corticotrophin-releasing hormone-induced excitability in a catecholaminergic neuronal
cell line
Authors: *A. W. LEE 1 , S. A. RABACCHI 2 , I. A. ANTONIJEVIC 2 , K. E. SMITH 2 , Q.
ZHANG 1 , L.-M. KOW 1 , D. W. PFAFF 1 ;
1 Neurobio. & Behavior, Rockefeller Univ., New York, NY; 2 Lundbeck Res. USA, Inc., Paramus,
NJ
Abstract: Hyperactivity of neurons secreting corticotrophin-releasing hormone (CRH) is a
serious condition that is likely to underlie the pathophysiology of many disorders. CRH regulates
the neuroendocrine stress response, resulting in stimulation of corticotrophin and subsequent
glucocorticoid secretion. The locus coeruleus is activated by stress, resulting in increased
noradrenaline secretion. CATH.a cells are a CNS catecholaminergic cell line immortalized from
the locus coeruleus. Patch clamp recordings were carried out in current clamp mode to examine
the effects of corticosterone (CORT), dexamethasone (DEX), CRH, or a combination DEX and
CRH on CATH.a cells. Bath application of DEX (1 or 2 µM, 5-10 min) or CORT (1 µM, 5-10
min) depolarized about one third of the cells. CRH alone at (1 or 10 µM, 3 min) reversibly
depolarized CATH.a cells. When the combination of DEX (1 µM) and various doses of CRH
(0.01 - 10 µM) was tested, there was a synergistic effect at the highest concentration of CRH;
DEX and CRH (10 µM) worked synergistically to depolarize the membrane potential to levels
more than 50% greater than DEX or CRH alone. Analysis of these cells by reverse
transcriptase/polymerase chain reaction revealed the presence of mRNAs for glucocorticoid
receptors and CRH receptors type 1 and 2. These data indicate that CATH.a cells are sensitive to
CRH, and that under acute DEX treatment, are still more sensitive to CRH. Current studies
address chronic exposure to glucocorticoids. Further studies are also being conducted on CAD
cells, a variant of CATH.a in which morphological differentiation can be initiated.
Disclosures: A.W. Lee, None; S.A. Rabacchi, None; I.A. Antonijevic, None; K.E. Smith,
None; Q. Zhang, None; L. Kow, None; D.W. Pfaff, None.
Poster
282. Stress and the Brain: Cellular Actions of Stress
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 282.13/OO20
Topic: E.06.d. Cellular actions of stress