TY - JOUR
T1 - Chronic morphine administration results in tolerance to delta opioid receptor-mediated antinociception
AU - Pradhan, A. A.A.
AU - Siau, C.
AU - Constantin, A.
AU - Clarke, P. B.S.
N1 - Funding Information:
We thank Jenni Slaven for technical expertise and AstraZeneca R&D Montreal for the generous gift of the radioligand [ 125 I]DELT. We would also like to thank Drs. F. Abbott and T. Coderre for the use of behavioral equipment. This work was supported by the Canadian Institutes of Health Research (CIHR, grant numbers: MOP-44053 and MOP-10516).
PY - 2006
Y1 - 2006
N2 - Delta opioid receptor agonists produce only a moderate degree of antinociception, possibly reflecting the predominantly intracellular location of delta opioid receptor. However, recent studies suggest that short term morphine pretreatment can increase delta opioid receptor-mediated antinociception by promoting the translocation of delta opioid receptor to the cell surface. Even more striking sensitization has been reported after long term morphine pretreatment and withdrawal in locomotor tests. In the present study we therefore examined the effects of longer term morphine pretreatment and withdrawal on delta opioid receptor-mediated antinociception in the formalin test. Male adult rats were pretreated daily with morphine (10 mg/kg s.c.) or saline for 10 days, and were tested acutely with the delta opioid receptor agonist [d-Ala2,Glu4]-deltorphin (intrathecal) at 0, 7 and 14 days of withdrawal. Unexpectedly, chronic morphine pre-exposure resulted in tolerance to [d-Ala2,Glu4]-deltorphin-induced antinociception, and this occurred at 0 and 7 but not 14 days of morphine withdrawal. Morphine challenge at withdrawal day 7 confirmed the presence of tolerance to the antinociceptive effects of this drug. Chronic morphine pretreatment also resulted in tolerance to the locomotor stimulant effect of [d-Ala2,Glu4]-deltorphin (given i.c.v.), contrary to a previous report of sensitization. However, consistent with previous reports, short term (2 day) pretreatment with morphine did result in sensitization to [d-Ala2,Glu4]-deltorphin. Subsequent in vitro analysis, using [125I][d-Ala2,Glu4]-deltorphin or guanosine 5′(γ-35S-thio) triphosphate autoradiography, did not reveal any changes in delta opioid receptor binding or function resulting from chronic morphine pretreatment. In conclusion, chronic morphine pretreatment caused tolerance to delta opioid receptor-mediated behavioral effects with no clear change at the receptor level.
AB - Delta opioid receptor agonists produce only a moderate degree of antinociception, possibly reflecting the predominantly intracellular location of delta opioid receptor. However, recent studies suggest that short term morphine pretreatment can increase delta opioid receptor-mediated antinociception by promoting the translocation of delta opioid receptor to the cell surface. Even more striking sensitization has been reported after long term morphine pretreatment and withdrawal in locomotor tests. In the present study we therefore examined the effects of longer term morphine pretreatment and withdrawal on delta opioid receptor-mediated antinociception in the formalin test. Male adult rats were pretreated daily with morphine (10 mg/kg s.c.) or saline for 10 days, and were tested acutely with the delta opioid receptor agonist [d-Ala2,Glu4]-deltorphin (intrathecal) at 0, 7 and 14 days of withdrawal. Unexpectedly, chronic morphine pre-exposure resulted in tolerance to [d-Ala2,Glu4]-deltorphin-induced antinociception, and this occurred at 0 and 7 but not 14 days of morphine withdrawal. Morphine challenge at withdrawal day 7 confirmed the presence of tolerance to the antinociceptive effects of this drug. Chronic morphine pretreatment also resulted in tolerance to the locomotor stimulant effect of [d-Ala2,Glu4]-deltorphin (given i.c.v.), contrary to a previous report of sensitization. However, consistent with previous reports, short term (2 day) pretreatment with morphine did result in sensitization to [d-Ala2,Glu4]-deltorphin. Subsequent in vitro analysis, using [125I][d-Ala2,Glu4]-deltorphin or guanosine 5′(γ-35S-thio) triphosphate autoradiography, did not reveal any changes in delta opioid receptor binding or function resulting from chronic morphine pretreatment. In conclusion, chronic morphine pretreatment caused tolerance to delta opioid receptor-mediated behavioral effects with no clear change at the receptor level.
KW - deltorphin II
KW - formalin
KW - locomotion
KW - mu opioid receptor
KW - withdrawal
UR - https://www.scopus.com/pages/publications/33746191720
U2 - 10.1016/j.neuroscience.2006.04.021
DO - 10.1016/j.neuroscience.2006.04.021
M3 - Article
C2 - 16716526
AN - SCOPUS:33746191720
SN - 0306-4522
VL - 141
SP - 947
EP - 954
JO - Neuroscience
JF - Neuroscience
IS - 2
ER -