Age-related differences in sensitivity to the antinociceptive effects of kappa opioids in adult male rats.
BACKGROUND
Significant differences in the potency and effectiveness of opioid analgesics have been reported in subject populations differing in age. Although the relationship between aging and sensitivity to the antinociceptive effects of mu opioids has been examined extensively, relatively few studies have examined this relationship in kappa opioids.


OBJECTIVE
The purpose of the present investigation was to examine the antinociceptive effects of selected kappa and mixed-action opioids in young (3 months) and aged (21 months) male rats.


METHODS
In a warm-water, tail-withdrawal procedure, rats were restrained and the latencies to remove their tails from 50 degrees C (low temperature) and 55 degrees C (high temperature) water were measured. Selected kappa (U69,593, U50,488) and mixed-action (butorphanol, nalbuphine) opioids were tested alone, and in combination with the high-efficacy, kappa-opioid spiradoline.


RESULTS
All test drugs were more effective (i.e., produced a greater maximal effect) in aged rats than in young rats at both water temperatures. In drug combination tests, U69,593 and U50,488 enhanced the effects of spiradoline under conditions in which they failed to produce high levels of antinociception when administered alone. In contrast, butorphanol and nalbuphine antagonized the effects of spiradoline under conditions in which they failed to produce high levels of antinociception when administered alone.


CONCLUSIONS
These data may be taken as evidence that: (1) aged male rats are more sensitive than young male rats to the antinociceptive effects of kappa opioids, (2) U69,593 and U50,488 display agonist activity in the warm-water, tail-withdrawal procedure under some conditions in which they fail to produce antinociceptive effects, and (3) butorphanol and nalbuphine possess only limited agonist activity at the kappa receptor.
Smith
Mark A
MA
Program in Neuroscience, Davidson College, Davidson, NC 28035-7037, USA. masmith@davidson.edu
French
Adam M
AM
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000367:Age Factors; D000700:Analgesics / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D044482:Benzeneacetamides; D002077:Butorphanol / Q000494:pharmacology; D003080:Cold Temperature; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D009266:Nalbuphine / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology / Q000517:prevention & control; D010147:Pain Measurement; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011930:Reaction Time; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000187:drug effects* / Q000502:physiology
D000700:Analgesics; D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D044482:Benzeneacetamides; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C045444:U 69593; D009266:Nalbuphine; C051272:spiradoline; D002077:Butorphanol