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Pharmacological Characterization of Morphine‐Induced In Vivo Release of Cholecystokinin in Rat Dorsal Horn
Author(s) -
Gustafsson Henrik,
Afrah Abdullahi,
Brodin Ernst,
Stiller CarlOlav
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0731145.x
Subject(s) - morphine , microdialysis , (+) naloxone , chemistry , verapamil , cholecystokinin , calcium channel blocker , pharmacology , nociception , calcium channel , voltage dependent calcium channel , opioid , spinal cord , calcium , channel blocker , medicine , endocrinology , extracellular , receptor , neuroscience , biology , biochemistry , organic chemistry
: Previous studies indicate that an increased release of cholecystokinin (CCK) in response to morphine administration may counteract opioid‐induced analgesia at the spinal level. In the present study we used in vivo microdialysis to demonstrate that systemic administration of antinociceptive doses of morphine (1‐5 mg/kg, s.c.) induces a dose‐dependent and naloxone‐reversible release of CCK‐like immunoreactivity (CCK‐LI) in the dorsal horn of the spinal cord. A similar response could also be observed following perfusion of the dialysis probe for 60 min with 100 μ M but not with 1 μ M morphine. The CCK‐LI release induced by morphine (5 mg/kg, s.c.) was found to be calcium‐dependent and tetrodotoxin‐sensitive (1 μ M in the perfusion medium). Topical application of either the L‐type calcium channel blocker verapamil (50 μg) or the N‐type calcium channel blocker ω‐conotoxin GVIA (0.4 μg) onto the dorsal spinal cord completely prevented the CCK‐LI release induced by morphine (5 mg/kg, s.c.). Our data indicate that activation of L ‐ and N‐type calcium channels is of importance for morphineinduced CCK release, even though the precise site of action of morphine in the dorsal horn remains unclear. The present findings also suggest a mechanism for the potentiation of opioid analgesia by L‐and N‐type calcium channel blocking agents.