11-20-2007, 10:41 PM
Abstract
Rationale Nociceptin/orphanin FQ (N/OFQ) has been proposed to be a functional antagonist of corticotropin-releasing factor (CRF) in
relation to its anti-stress action and its ability to antagonize the anorectic effect of CRF in rats without exhibiting affinity
for CRF receptors. The bed nucleus of the stria terminalis (BST) is highly sensitive to the inhibitory effect of N/OFQ on
CRF-induced anorexia.
Objective The present study was aimed at further evaluating the role of the BST in the functional antagonism between N/OFQ and CRF by
examining it at molecular level and in the context of CRF-induced anxiety in the rat.
Materials and methods First, in situ hybridization experiments investigated the expression of the pro-N/OFQ precursor and of NOP receptors in several
brain areas 6 h after injection of CRF (0.2 and 1 μg/rat) into the lateral cerebroventricle (LV). Second, the elevated plus
maze test was used to evaluate whether N/OFQ, injected into the BST (0.05 and 0.5 μg/rat) or into the LV (0.5, 1.8, and 2.4 μg/rat),
inhibits the anxiogenic-like effect evoked by LV injection of CRF (1 μg/rat) in rats.
Results The in situ hybridization study showed that LV injection of CRF 1 μg/rat increases NOP receptor expression in the BST, while
no change of the N/OFQ precursor was observed. On the other hand, N/OFQ injection into the BST blocks the anxiogenic effect
of CRF at doses lower than those required by LV injection (0.5 vs 1.8 μg/rat, respectively).
Conclusion These data provide further support for the hypothesis that N/OFQ may behave as functional antagonist of CRF and suggest that
this antagonism may occur within the BST.
Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00213-007-0985-7Authors
Donata Rodi, University of Ferrara Department of Clinical and Experimental Medicine, Pharmacology Section, and Neuroscience Centre 44100 Ferrara ItalySilvia Zucchini, University of Ferrara Department of Clinical and Experimental Medicine, Pharmacology Section, and Neuroscience Centre 44100 Ferrara ItalyMichele Simonato, University of Ferrara Department of Clinical and Experimental Medicine, Pharmacology Section, and Neuroscience Centre 44100 Ferrara ItalyCarlo Cifani, University of Camerino Department of Experimental Medicine and Public Health Via Scalzino 5 62032 Camerino (MC) ItalyMaurizio Massi, University of Camerino Department of Experimental Medicine and Public Health Via Scalzino 5 62032 Camerino (MC) ItalyCarlo Polidori, University of Camerino Department of Experimental Medicine and Public Health Via Scalzino 5 62032 Camerino (MC) Italy
Journal PsychopharmacologyOnline ISSN 1432-2072Print ISSN 0033-3158 (Source: Psychopharmacology)
Posted on Thu, 08 Nov 2007 16:08:22 +0100 at http://www.springerlink.com/content/124765615615v2u1/
Author: Psychopharmacology
Comments: http://www.medworm.com/rss/comments.php?id=1017012
Rationale Nociceptin/orphanin FQ (N/OFQ) has been proposed to be a functional antagonist of corticotropin-releasing factor (CRF) in
relation to its anti-stress action and its ability to antagonize the anorectic effect of CRF in rats without exhibiting affinity
for CRF receptors. The bed nucleus of the stria terminalis (BST) is highly sensitive to the inhibitory effect of N/OFQ on
CRF-induced anorexia.
Objective The present study was aimed at further evaluating the role of the BST in the functional antagonism between N/OFQ and CRF by
examining it at molecular level and in the context of CRF-induced anxiety in the rat.
Materials and methods First, in situ hybridization experiments investigated the expression of the pro-N/OFQ precursor and of NOP receptors in several
brain areas 6 h after injection of CRF (0.2 and 1 μg/rat) into the lateral cerebroventricle (LV). Second, the elevated plus
maze test was used to evaluate whether N/OFQ, injected into the BST (0.05 and 0.5 μg/rat) or into the LV (0.5, 1.8, and 2.4 μg/rat),
inhibits the anxiogenic-like effect evoked by LV injection of CRF (1 μg/rat) in rats.
Results The in situ hybridization study showed that LV injection of CRF 1 μg/rat increases NOP receptor expression in the BST, while
no change of the N/OFQ precursor was observed. On the other hand, N/OFQ injection into the BST blocks the anxiogenic effect
of CRF at doses lower than those required by LV injection (0.5 vs 1.8 μg/rat, respectively).
Conclusion These data provide further support for the hypothesis that N/OFQ may behave as functional antagonist of CRF and suggest that
this antagonism may occur within the BST.
Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00213-007-0985-7Authors
Donata Rodi, University of Ferrara Department of Clinical and Experimental Medicine, Pharmacology Section, and Neuroscience Centre 44100 Ferrara ItalySilvia Zucchini, University of Ferrara Department of Clinical and Experimental Medicine, Pharmacology Section, and Neuroscience Centre 44100 Ferrara ItalyMichele Simonato, University of Ferrara Department of Clinical and Experimental Medicine, Pharmacology Section, and Neuroscience Centre 44100 Ferrara ItalyCarlo Cifani, University of Camerino Department of Experimental Medicine and Public Health Via Scalzino 5 62032 Camerino (MC) ItalyMaurizio Massi, University of Camerino Department of Experimental Medicine and Public Health Via Scalzino 5 62032 Camerino (MC) ItalyCarlo Polidori, University of Camerino Department of Experimental Medicine and Public Health Via Scalzino 5 62032 Camerino (MC) Italy
Journal PsychopharmacologyOnline ISSN 1432-2072Print ISSN 0033-3158 (Source: Psychopharmacology)
Posted on Thu, 08 Nov 2007 16:08:22 +0100 at http://www.springerlink.com/content/124765615615v2u1/
Author: Psychopharmacology
Comments: http://www.medworm.com/rss/comments.php?id=1017012