δ-Opioid receptor-mediated increase in cortical extracellular levels of cholecystokinin-like material by subchronic morphine in rats

• Published in: Neuropharmacology Vol. 39; no. 2; pp. 161 - 171
• Main Authors: Becker, Chrystel, Pohl, Michel, Thiébot, Marie-Hélène, Collin, Elisabeth, Hamon, Michel, Cesselin, François, Benoliel, Jean-Jacques
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-01-2000; Elsevier
• Subjects: Analgesics; Analgesics, Opioid - pharmacology; Animals; Biological and medical sciences; Cholecystokinin - metabolism; Cholecystokinin like-material; Drug Interactions; Drug Tolerance; Frontal cortex; Male; Medical sciences; Microdialysis; Morphine - pharmacology; Morphine tolerance; Narcotic Antagonists - pharmacology; Neuropharmacology; Opioid receptors; Pharmacology. Drug treatments; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Protein Precursors - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Opioid, delta - antagonists & inhibitors; Receptors, Opioid, delta - metabolism; RNA, Messenger - metabolism; RT-PCR; CCK-8S, sulphated CCK-8; Morphine tolerance; BSA, bovine serum albumin; Cholecystokinin like-material; LM, like-material; Opioid receptors; CCK, cholecystokinin; O.D., optical density; Frontal cortex; RB 101, N-{( R, S)-2-benzyl-3[( S)(2-amino-4-methylthio)butyldithio]-1-oxopropyl}- l-phenylalanine benzyl ester; DTLET, Tyr- d-Thr-Gly-Phe-Leu-Thr; Microdialysis; nor-BNI, nor-binaltorphimine; BUBUC, H-Tyr- d-Cys(StBu)-Gly-Phe-Leu-Thr(OtBu)-OH; RT-PCR; aCSF, artificial cerebrospinal fluid; BNTX, 7-benzylidenenaltrexone; NTB, naltriben; RIA, radioimmunoassay; CTOP, d-Phe-Cys-Tyr- d-Trp-Orn-Thr-Pen-Thr-NH 2; Rat; Opioid receptor; Rodentia; Central nervous system; Tolerance; Morphine; Narcotic analgesic; Gene expression; δ Opioid receptor; Analgesia; Vertebrata; Mammalia; Animal; Subcutaneous administration; Antagonist; Cholecystokinin; Mechanism of action; Brain (vertebrata)
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/S0028-3908(99)00161-6

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 μM). The opioid receptors responsible for morphine-induced cortical CCKLM overflow appeared to be of the
δ type because intracortical infusion of selective
δ-opioid receptor antagonists such as naltriben (10 μM) and 7-benzylidenenaltrexone (10 μM) also prevented the effect of morphine, whereas CTOP (10 μM), a selective
μ-opioid receptor antagonist, and nor-binaltorphimine (10 μM), a selective
κ-opioid receptor antagonist, were inactive. These data indicate that morphine tolerance is associated with
δ-opioid receptor mediated activation of cortical CCKergic systems in rats.