Increased neuropeptide-converting enzyme activities in cerebrospinal fluid of opiate-tolerant rats.
Rats were given a continuous subcutaneous infusion at constant rate with either morphine, the opioid agonist/antagonist analgesic dezocine or saline. Tolerance to the antinociceptive effect of morphine or dezocine was complete on day 8, when cisterna magnum cerebrospinal fluid (CSF) was sampled under anesthesia. The activity of the enzymes cleaving dynorphin A (DCE) and substance P (SPE) was measured in the CSF. It was found that the animals treated with morphine had a 2- to 3-fold increase in both DCE and SPE activities. The animals treated with dezocine showed a similar increase in the activity of DCE, whereas SPE did not significantly change. These enzymes may therefore play a role in the development of tolerance to opioid analgesic drugs. The experiments show that chronic opioid treatment affects peptidergic mechanisms.
Persson
S
S
Department of Pharmacology, University of Uppsala, Sweden.
Post
C
C
Alari
L
L
Nyberg
F
F
Terenius
L
L
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003516:Cycloparaffins / Q000494:pharmacology*; D004361:Drug Tolerance; D004399:Dynorphins / Q000378:metabolism*; D008297:Male; D008666:Metalloendopeptidases / Q000134:cerebrospinal fluid*; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012697:Serine Endopeptidases / Q000134:cerebrospinal fluid*; D013373:Substance P / Q000378:metabolism*; D013764:Tetrahydronaphthalenes
D019086:Bridged Bicyclo Compounds, Heterocyclic; D003516:Cycloparaffins; D013764:Tetrahydronaphthalenes; D013373:Substance P; D004399:Dynorphins; D009020:Morphine; D012697:Serine Endopeptidases; C054870:dynorphin-converting endopeptidase; D008666:Metalloendopeptidases; C029610:substance P degrading enzyme; C010827:dezocine