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Functional antagonism between nociceptin/orphanin FQ (N/OFQ) and corticotropin-releasing factor (CRF) in the rat brain: evidence for involvement of the bed nucleus of the stria terminalis

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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.

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Acknowledgement

This study was supported by the MURST (COFIN 2004 to Prof. Maurizio Massi). We wish to thank Sheila Beatty for the stylistic corrections of the manuscript.

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, Pharmacology Section, and Neuroscience Centre, University of Ferrara, 44100, Ferrara, Italy

    Donata Rodi, Silvia Zucchini & Michele Simonato

  2. Department of Experimental Medicine and Public Health, University of Camerino, Via Scalzino 5, 62032, Camerino (MC), Italy

    Carlo Cifani, Maurizio Massi & Carlo Polidori

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  1. Donata Rodi
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  2. Silvia Zucchini
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  3. Michele Simonato
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  4. Carlo Cifani
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  5. Maurizio Massi
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Correspondence to Carlo Polidori.

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Rodi, D., Zucchini, S., Simonato, M. et al. Functional antagonism between nociceptin/orphanin FQ (N/OFQ) and corticotropin-releasing factor (CRF) in the rat brain: evidence for involvement of the bed nucleus of the stria terminalis. Psychopharmacology 196, 523–531 (2008). https://doi.org/10.1007/s00213-007-0985-7

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