Cholecystokinin gene expression in rat amygdaloid neurons: normal distribution and effect of morphine tolerance.
Previous studies have shown that repeated opioid administration induces a tolerance to opioid, presumably due in part to an opioid-mediated compensatory increase in brain cholecystokinin (CCK) synthesis and/or release. In this study, in situ hybridization histochemistry was used to examine the effect of morphine tolerance on CCK gene expression in the amygdala of rat brains, by using a 35S-labeled synthetic oligonucleotide probe. CCK mRNA-positive neurons in normal rats were seen throughout the amygdaloid complex, with the most heavily labeled neurons in lateral, basal, and cortical nuclei, followed by the medial nucleus. Only a few labeled neurons were found in central and intercalated nuclei. The development of morphine tolerance in the rat was associated with increased hybridization signals for CCK mRNA in each subnucleus of the amygdala. Increases were seen in the numbers of positively labeled neurons and/or the numbers of hybridization grains per positively labeled neuron. Furthermore, differential patterns of increase in CCK mRNA in morphine tolerant rats occurred in different subnuclei of the amygdala, with the highest magnitude of increase in the cortical nucleus, followed in order by the medial, central, basal, intercalated and lateral nuclei. The present study demonstrated that repeated administration of morphine increased CCK gene expression in the amygdaloid complex, and suggested that the development of the tolerance to morphine analgesia is due, in part, to an increase in CCK activity in the amygdaloid complex. These findings substantiate the hypothesis that long-term administration of opioid may induce a compensatory increase in CCK synthesis and/or release, which then results in a progressive antagonism of opioid analgesia.
Pu
S
S
Department of Physiology, First School of Clinical Medicine, Beijing Medical University, People's Republic of China.
Zhuang
H
H
Lu
Z
Z
Wu
X
X
Han
J
J
D000679:Amygdala / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002766:Cholecystokinin / Q000235:genetics*; D004361:Drug Tolerance; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values
D009020:Morphine; D002766:Cholecystokinin