Impaired supersensitivity to morphine following chronic naltrexone treatment in senescent rats

Janet L. Neisewander, Arthur J. Nonneman, James K. Rowlett, Michael T. Bardo

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Chronic administration of opiate antagonists produces an increase in the density of opiate receptors, as well as an enhanced sensitivity to the analgesic and locomotor depressant effects of morphine. The present study assessed whether aging alters these regulatory processes. Young (3-4 months), middle-aged (10-11 months), and senescent (25-30 months) rats were implanted subdermally with slow-release naltrexone pellets or were given sham surgery. The pellets were removed 10 days later. Twenty-four hours after pellet removal, morphine-induced (5 mg/kg, SC) analgesia and locomotor activity were assessed. Young and middle-aged rats treated with naltrexone showed enhanced sensitivity to the analgesic and locomotor activity depressant effects of morphine relative to age-matched controls. In contrast, senescent rats treated with naltrexone did not differ from age-matched controls in their response to morphine. The density of opiate receptors labeled with 3H-naloxone was measured in the anterior striatum. Both young and senescent rats treated with naltrexone exhibited an increase in opiate receptor density relative to age-matched controls. The results indicate that senescent rats are capable of up-regulating opiate receptors following chronic naltrexone treatment but not exhibit the correxponding functional supersensitivity to morphine.

Original languageEnglish (US)
Pages (from-to)91-97
Number of pages7
JournalNeurobiology of Aging
Volume15
Issue number1
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

Keywords

  • Aging
  • Analgesia
  • Behavioral supersensitivity
  • Hot plate test
  • Locomotor activity
  • Morphine
  • Naltrexone
  • Opiate antagonist
  • Opiate receptors
  • Receptor regulation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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