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The nociceptin/orphanin FQ antagonist UFP-101 differentially modulates the glucocorticoid response to restraint stress in rats during the peak and nadir phases of the hypothalamo-pituitary-adrenal axis circadian rhythm.
Neuroscience 2007; 147(3):757-64N

Abstract

The involvement of nociceptin (N/OFQ) and the nociceptin/orphanin FQ peptide (NOP) receptor in behavior associated with stress and anxiety has been established but their role in the regulation of the hypothalamo-pituitary-adrenal (HPA) axis under conditions of stress has not been fully investigated. We used the selective NOP receptor antagonist UFP-101 to examine the contribution of endogenous N/OFQ to HPA axis control under conditions of restraint stress in the morning and the evening. We found that in the morning during the HPA axis circadian nadir rats exposed to restraint stress in both the presence and absence of UFP-101 exhibited significantly elevated plasma corticosterone at 30 min post-i.c.v. injection compared to the home cage control group. Additionally, rats treated with UFP-101 and exposed to restraint had significantly elevated corticosterone levels at 60 min post-i.c.v. injection compared to all other treatment groups. Interestingly, while there was a significant increase in the expression of CRF mRNA in the paraventricular nucleus (PVN) of rats exposed to restraint stress only, there was no comparable increase in those co-treated with UFP-101. There was no change in the expression of AVP or POMC mRNA in any of the treatment groups. In contrast, when carried out in the evening we observed significantly elevated plasma corticosterone in the vehicle-treated restraint group only at 30 min post-i.c.v. injection. There was no significant difference between the UFP-101-treated restraint group and either of the home cage control groups or the vehicle-treated restraint group. Additionally, in contrast to the morning study, UFP-101 did not prolong glucocorticoid release at the 60 min time-point. These results demonstrate for the first time a differential effect of UFP-101 on restraint stress-induced HPA axis activity characterized by significant prolongation of stress-induced activity in the morning but no significant effect on the response to restraint in the evening.

Authors+Show Affiliations

Department of Anatomy, University of Bristol, Southwell Street, Bristol, UK.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17574767

Citation

Leggett, J D., et al. "The Nociceptin/orphanin FQ Antagonist UFP-101 Differentially Modulates the Glucocorticoid Response to Restraint Stress in Rats During the Peak and Nadir Phases of the Hypothalamo-pituitary-adrenal Axis Circadian Rhythm." Neuroscience, vol. 147, no. 3, 2007, pp. 757-64.
Leggett JD, Jessop DS, Fulford AJ. The nociceptin/orphanin FQ antagonist UFP-101 differentially modulates the glucocorticoid response to restraint stress in rats during the peak and nadir phases of the hypothalamo-pituitary-adrenal axis circadian rhythm. Neuroscience. 2007;147(3):757-64.
Leggett, J. D., Jessop, D. S., & Fulford, A. J. (2007). The nociceptin/orphanin FQ antagonist UFP-101 differentially modulates the glucocorticoid response to restraint stress in rats during the peak and nadir phases of the hypothalamo-pituitary-adrenal axis circadian rhythm. Neuroscience, 147(3), pp. 757-64.
Leggett JD, Jessop DS, Fulford AJ. The Nociceptin/orphanin FQ Antagonist UFP-101 Differentially Modulates the Glucocorticoid Response to Restraint Stress in Rats During the Peak and Nadir Phases of the Hypothalamo-pituitary-adrenal Axis Circadian Rhythm. Neuroscience. 2007 Jul 13;147(3):757-64. PubMed PMID: 17574767.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The nociceptin/orphanin FQ antagonist UFP-101 differentially modulates the glucocorticoid response to restraint stress in rats during the peak and nadir phases of the hypothalamo-pituitary-adrenal axis circadian rhythm. AU - Leggett,J D, AU - Jessop,D S, AU - Fulford,A J, Y1 - 2007/06/15/ PY - 2007/01/08/received PY - 2007/04/04/revised PY - 2007/04/05/accepted PY - 2007/6/19/pubmed PY - 2007/10/20/medline PY - 2007/6/19/entrez SP - 757 EP - 64 JF - Neuroscience JO - Neuroscience VL - 147 IS - 3 N2 - The involvement of nociceptin (N/OFQ) and the nociceptin/orphanin FQ peptide (NOP) receptor in behavior associated with stress and anxiety has been established but their role in the regulation of the hypothalamo-pituitary-adrenal (HPA) axis under conditions of stress has not been fully investigated. We used the selective NOP receptor antagonist UFP-101 to examine the contribution of endogenous N/OFQ to HPA axis control under conditions of restraint stress in the morning and the evening. We found that in the morning during the HPA axis circadian nadir rats exposed to restraint stress in both the presence and absence of UFP-101 exhibited significantly elevated plasma corticosterone at 30 min post-i.c.v. injection compared to the home cage control group. Additionally, rats treated with UFP-101 and exposed to restraint had significantly elevated corticosterone levels at 60 min post-i.c.v. injection compared to all other treatment groups. Interestingly, while there was a significant increase in the expression of CRF mRNA in the paraventricular nucleus (PVN) of rats exposed to restraint stress only, there was no comparable increase in those co-treated with UFP-101. There was no change in the expression of AVP or POMC mRNA in any of the treatment groups. In contrast, when carried out in the evening we observed significantly elevated plasma corticosterone in the vehicle-treated restraint group only at 30 min post-i.c.v. injection. There was no significant difference between the UFP-101-treated restraint group and either of the home cage control groups or the vehicle-treated restraint group. Additionally, in contrast to the morning study, UFP-101 did not prolong glucocorticoid release at the 60 min time-point. These results demonstrate for the first time a differential effect of UFP-101 on restraint stress-induced HPA axis activity characterized by significant prolongation of stress-induced activity in the morning but no significant effect on the response to restraint in the evening. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/17574767/The_nociceptin/orphanin_FQ_antagonist_UFP_101_differentially_modulates_the_glucocorticoid_response_to_restraint_stress_in_rats_during_the_peak_and_nadir_phases_of_the_hypothalamo_pituitary_adrenal_axis_circadian_rhythm_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(07)00471-X DB - PRIME DP - Unbound Medicine ER -