TY - JOUR
T1 - The behavioral phenotype of pituitary adenylate-cyclase activating polypeptide-deficient mice in anxiety and depression tests is accompanied by blunted c-Fos expression in the bed nucleus of the stria terminalis, central projecting Edinger-Westphal nucleus, ventral lateral septum, and dorsal raphe nucleus
AU - Gaszner, B.
AU - Kormos, V.
AU - Kozicz, T.
AU - Hashimoto, H.
AU - Reglodi, D.
AU - Helyes, Z.
N1 - Funding Information:
This work was supported by Hungarian Grants OTKA K72592 , K73044 , NK78059 , CNK78480 , “Science, Please! Research Teams on Innovation” programme ( SROP-4.2.2/08/1/2008-0011 ), Developing Competitiveness of Universities in the South Transdanubian Region ( SROP-4.2.1.B-10/2/KONV-2010-0002 ) and “Lendulet” Programme of the Hungarian Academy of Sciences . H. Hashimoto was supported by grants-in-aid for Scientific Research from Japan Society for the Promotion of Science (JSPS) and the Funding Program for Next Generation World-Leading Researchers . B. Gaszner was supported by the Bolyai Postdoctoral Research Fellowship and by a research grants of Pécs University ( PTE KA-34039/10-8 ) and OTKA PD100706 .
PY - 2012/1/27
Y1 - 2012/1/27
N2 - Pituitary adenylate-cyclase activating polypeptide (PACAP) has been implicated in the (patho)physiology of stress-adaptation. PACAP deficient (PACAP -/-) mice show altered anxiety levels and depression-like behavior, but little is known about the underlying mechanisms in stress-related brain areas. Therefore, we aimed at investigating PACAP -/- mice in light-dark box, marble burying, open field, and forced swim paradigms. We also analyzed whether the forced swim test-induced c-Fos expression would be affected by PACAP deficiency in the following stress-related brain areas: magno- and parvocellular paraventricular nucleus of the hypothalamus (PVN); basolateral (BLA), medial (MeA), and central (CeA) amygdaloid nuclei; ventral (BSTv), dorsolateral (BSTdl), dorsomedial (BSTdm), and oval (BSTov) nuclei of the bed nucleus of stria terminalis; dorsal (dLS) and ventral parts (vLS) of lateral septal nucleus, central projecting Edinger-Westphal nucleus (EWcp), dorsal (dPAG) and lateral (lPAG) periaqueductal gray matter, dorsal raphe nucleus (DR). Our results revealed that PACAP -/- mice showed greatly reduced anxiety and increased locomotor activity compared with wildtypes. In forced swim test PACAP -/- mice showed increased depression-like behavior. Forced swim exposure increased c-Fos expression in all examined brain areas in wildtypes, whereas this was markedly blunted in the DR, EWcp, BSTov, BSTdl, BSTv, PVN, vLS, dPAG, and in the lPAG of PACAP -/- mice vs. wildtypes, strongly suggesting their involvement in the behavioral phenotype of PACAP -/- mice. PACAP deficiency did not influence the c-Fos response in the CeA, MeA, BSTdm, and dLS. Therefore, we propose that PACAP exerts a brain area-specific effect on stress-induced neuronal activation and it might contribute to stress-related mood disorders.
AB - Pituitary adenylate-cyclase activating polypeptide (PACAP) has been implicated in the (patho)physiology of stress-adaptation. PACAP deficient (PACAP -/-) mice show altered anxiety levels and depression-like behavior, but little is known about the underlying mechanisms in stress-related brain areas. Therefore, we aimed at investigating PACAP -/- mice in light-dark box, marble burying, open field, and forced swim paradigms. We also analyzed whether the forced swim test-induced c-Fos expression would be affected by PACAP deficiency in the following stress-related brain areas: magno- and parvocellular paraventricular nucleus of the hypothalamus (PVN); basolateral (BLA), medial (MeA), and central (CeA) amygdaloid nuclei; ventral (BSTv), dorsolateral (BSTdl), dorsomedial (BSTdm), and oval (BSTov) nuclei of the bed nucleus of stria terminalis; dorsal (dLS) and ventral parts (vLS) of lateral septal nucleus, central projecting Edinger-Westphal nucleus (EWcp), dorsal (dPAG) and lateral (lPAG) periaqueductal gray matter, dorsal raphe nucleus (DR). Our results revealed that PACAP -/- mice showed greatly reduced anxiety and increased locomotor activity compared with wildtypes. In forced swim test PACAP -/- mice showed increased depression-like behavior. Forced swim exposure increased c-Fos expression in all examined brain areas in wildtypes, whereas this was markedly blunted in the DR, EWcp, BSTov, BSTdl, BSTv, PVN, vLS, dPAG, and in the lPAG of PACAP -/- mice vs. wildtypes, strongly suggesting their involvement in the behavioral phenotype of PACAP -/- mice. PACAP deficiency did not influence the c-Fos response in the CeA, MeA, BSTdm, and dLS. Therefore, we propose that PACAP exerts a brain area-specific effect on stress-induced neuronal activation and it might contribute to stress-related mood disorders.
KW - Amygdala
KW - Bed nucleus of stria terminalis
KW - Dorsal raphe nucleus
KW - Edinger-Westphal nucleus
KW - Hypothalmic paraventricular nucleus
KW - Stress
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U2 - 10.1016/j.neuroscience.2011.11.046
DO - 10.1016/j.neuroscience.2011.11.046
M3 - Article
C2 - 22178610
AN - SCOPUS:84856231983
SN - 0306-4522
VL - 202
SP - 283
EP - 299
JO - Neuroscience
JF - Neuroscience
ER -