Delta(2)-opioid receptor mediation of morphine-induced CCK release in the frontal cortex of the freely moving rat.
Numerous pharmacological data have been accumulated in support of the existence of physiological interactions between cholecystokinin (CCK) and opioids in the central nervous system. With the aim of further characterizing these interactions, an in vivo microdialysis approach was used to directly assess the possible influence of opioids on the extracellular levels of CCK-like material (CCKLM) in the frontal cortex of the awake, freely moving rat. Systemic administration of a high dose of morphine (10 mg/kg i.p.) produced a marked increase (up to +200%) of cortical CCKLM outflow, and this effect could be completely prevented by systemic (1.5 mg/kg i.p.) as well as intracortical (10 microM) administration of the opioid receptor antagonist naloxone. The opioid receptors activated by morphine appeared to be of the delta type because the intracortical infusion of naltrindole (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 kappa-opioid receptor antagonist, were inactive. In addition, naltriben (10 microM), which acts selectively at the delta(2) subtype, also abolished the stimulatory effect of morphine on cortical CCKLM outflow, whereas 7-benzylidenenaltrexone (10 microM), a selective delta(1)-opioid receptor antagonist (10 microM), did not alter the morphine effect. Conversely, the direct stimulation of cortical delta(2)-opioid receptors by local infusion of [D-Ala(2)] deltorphin II mimicked the stimulatory effect of systemic morphine on CCKLM outflow. These data indicate that delta(2)-opioid receptors play a key role in opioid-CCK interactions in the rat frontal cortex.
Becker
C
C
INSERM U. 288, NeuroPsychoPharmacologie Moléculaire, Cellulaire et Fonctionnelle, Paris, France. becker@ext.jussieu.fr
Hamon
M
M
Cesselin
F
F
Benoliel
J J
JJ
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002766:Cholecystokinin / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D007267:Injections; D008024:Ligands; D008297:Male; D017551:Microdialysis; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology
D000701:Analgesics, Opioid; D008024:Ligands; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; C051844:norbinaltorphimine; D013004:Somatostatin; D009271:Naltrexone; D009020:Morphine; D002766:Cholecystokinin