Age-related differences in sensitivity to the antinociceptive effects of opioids in male rats - Influence of nociceptive intensity and intrinsic efficacy at the mu receptor

Citation
Ma. Smith et Jd. Gray, Age-related differences in sensitivity to the antinociceptive effects of opioids in male rats - Influence of nociceptive intensity and intrinsic efficacy at the mu receptor, PSYCHOPHAR, 156(4), 2001, pp. 445-453
Citations number
59
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
Volume
156
Issue
4
Year of publication
2001
Pages
445 - 453
Database
ISI
SICI code
Abstract
Rationale: Despite the widespread popularity of opioid analgesics, signific ant differences in the potency and effectiveness of these drugs are often o bserved across age groups. Objectives: The purpose of this investigation wa s to examine age-related differences in sensitivity to the antinociceptive effects of mu opioids and to identify the conditions under which these diff erences are most apparent. Methods: In a warm-water tail-withdrawal procedu re, young (3 months) and aged (24 months) male rats were habituated to rest raint and the latencies to remove their tails from 50 degreesC (low nocicep tive intensity) and 55 degreesC (high nociceptive intensity) water were mea sured. Opioids possessing a range of intrinsic efficacy at the mu receptor (morphine, levorphanol, buprenorphine, butorphanol, nalbuphine, nalorphine) were examined. Results: Young and aged rats were equally sensitive to the antinociceptive effects of morphine, levorphanol, and buprenorphine when te sted at the low nociceptive intensity. When these drugs were tested at the high nociceptive intensity, differences between the two age groups became a pparent, such that aged rats were significantly more sensitive to the antin ociceptive effects of these drugs than young rats. Differences between age groups were most apparent when butorphanol, nalbuphine, and nalorphine were tested, in that each of these drugs produced maximal levels of antinocicep tion in aged rats under conditions in which they failed to produce antinoci ceptive activity in young rats. Under conditions in which lower efficacy op ioids failed to produce antinociceptive activity in young rats, they antago nized the effects of morphine in drug combination tests. Conclusions: These data may be taken as evidence that aged male rats are more sensitive to th e antinociceptive effects of mu opioids than young male rats, and that age- related differences in opioid sensitivity are most apparent when lower effi cacy opioids and higher nociceptive intensities are employed during behavio ral testing.