In:
British Journal of Pharmacology, Wiley, Vol. 172, No. 14 ( 2015-07), p. 3638-3649
Abstract:
Opioids affect the circadian clock and may change the timing of many physiological processes. This study was undertaken to investigate the daily changes in sensitivity of the circadian pacemaker to an analgesic dose of morphine, and to uncover a possible interplay between circadian and opioid signalling. Experimental Approach A time‐dependent effect of morphine (1 mg·kg −1 , i.p.) applied either during the day or during the early night was followed, and the levels of phosphorylated ERK 1/2, GSK 3β, c‐Fos and Per genes were assessed by immunohistochemistry and in situ hybridization. The effect of morphine pretreatment on light‐induced pERK and c‐ F os was examined, and day/night difference in activity of opioid receptors was evaluated by [ 35 S]‐ GTP γS binding assay. Key Results Morphine stimulated a rise in pERK 1/2 and p GSK 3β levels in the suprachiasmatic nucleus ( SCN ) when applied during the day but significantly reduced both kinases when applied during the night. Morphine at night transiently induced Period1 but not Period2 in the SCN and did not attenuate the light‐induced level of pERK1/2 and c‐Fos in the SCN . The activity of all three principal opioid receptors was high during the day but decreased significantly at night, except for the δ receptor. Finally, we demonstrated daily profiles of p ERK 1/2 and p GSK 3β levels in the rat ventrolateral and dorsomedial SCN . Conclusions and Implications Our data suggest that the phase‐shifting effect of opioids may be mediated via post‐translational modification of clock proteins by means of activated ERK 1/2 and GSK 3β.
Type of Medium:
Online Resource
ISSN:
0007-1188
,
1476-5381
DOI:
10.1111/bph.2015.172.issue-14
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2029728-2
SSG:
15,3
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