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.
BACKGROUND
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.


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 microg/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 microg/rat) or into the LV (0.5, 1.8, and 2.4 microg/rat), inhibits the anxiogenic-like effect evoked by LV injection of CRF (1 microg/rat) in rats.


RESULTS
The in situ hybridization study showed that LV injection of CRF 1 microg/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 microg/rat, respectively).


CONCLUSIONS
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.
Rodi
Donata
D
Department of Clinical and Experimental Medicine, Pharmacology Section, and Neuroscience Centre, University of Ferrara, 44100 Ferrara, Italy.
Zucchini
Silvia
S
Simonato
Michele
M
Cifani
Carlo
C
Massi
Maurizio
M
Polidori
Carlo
C
D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology / Q000502:physiology*; D017403:In Situ Hybridization; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning; D018847:Opioid Peptides / Q000096:biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000096:biosynthesis; D012686:Septal Nuclei / Q000378:metabolism / Q000502:physiology*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D003346:Corticotropin-Releasing Hormone; D018847:Opioid Peptides; D012333:RNA, Messenger; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722285:Oprl1 protein, rat