Delta-opioid receptor-mediated increase in cortical extracellular levels of cholecystokinin-like material by subchronic morphine in rats.
Numerous pharmacological data indirectly support the idea that interactions between cholecystokinin (CCK) and opioids participate in the development of tolerance to morphine. Biochemical investigations were performed with the aim of directly assessing the status of such interactions in morphine treated rats. Tolerance to the alkaloid after s.c. implantation of morphine pellets for three days was not associated with any change in the levels of both CCK like-material (CCKLM) and proCCK mRNA in the frontal cortex. However, microdialysis in the freely moving rat showed that this morphine treatment produced a significant increase (+40%) of the cortical spontaneous CCKLM outflow, which could be completely prevented by intracortical infusion of naloxone (10 microM). The opioid receptors responsible for morphine-induced cortical CCKLM overflow appeared to be of the delta type because intracortical infusion of selective delta-opioid receptor antagonists such as naltriben (10 microM) and 7-benzylidenenaltrexone (10 microM) also prevented the effect of morphine, whereas CTOP (10 microM), a selective mu-opioid receptor antagonist, and nor-binaltorphimine (10 microM), a selective K-opioid receptor antagonist, were inactive. These data indicate that morphine tolerance is associated with delta-opioid receptor mediated activation of cortical CCKergic systems in rats.
Becker
C
C
INSERM U. 288, NeuroPsychoPharmacologie Moléculaire, Cellulaire et Fonctionnelle, C.H.U. Pitié-Salpêtrière, Paris, France. becker@idf.jussieu.fr
Pohl
M
M
Thiébot
M H
MH
Collin
E
E
Hamon
M
M
Cesselin
F
F
Benoliel
J J
JJ
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D002766:Cholecystokinin / Q000378:metabolism*; D004347:Drug Interactions; D004361:Drug Tolerance; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D011498:Protein Precursors; D012333:RNA, Messenger; D017465:Receptors, Opioid, delta; D009020:Morphine; C060249:procholecystokinin; D002766:Cholecystokinin