Stress-produced analgesia and morphine-produced analgesia: Lack of cross-tolerance

Richard J. Bodnar, Dennis D. Kelly, Solomon S. Steiner, Murray Glusman

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156 Scopus citations


Animals exposed to cold-water swims, rotation, inescapable shocks, abrupt food deprivation and other stressors display temporary analgesia. Since repeated exposures result in adaptation of this analgesia in much the same way that repeated administration of opiates results in tolerance, the possibility of cross-tolerance between cold-water stress-induced and morphine-induced analgesia was investigated. Flinch-jump thresholds were determined in ten experimental groups of six rats each. Three groups showed dose-dependent analgesia following single injections of morphine at 5, 10 and 15 mg/kg, respectively. A fourth group, subjected to a single cold-water swim at 2°C for 3.5 min, displayed analgesia comparable to that produced by 10 mg/kg of morphine. Groups subjected either to 14 daily cold-water swims or to 14 daily morphine injections at 10 mg/kg showed normal thresholds on the 14th day indicating that adaptation and tolerance had developed, respectively. The cross-over groups were exposed to either 13 days of cold-water swims followed by morphine or the reverse arrangement. Both groups showed profound analgesia instead of cross-tolerance, suggesting that a non-opiate neural mechanism may mediate stress-induced analgesia.

Original languageEnglish
Pages (from-to)661-666
Number of pages6
JournalPharmacology Biochemistry and Behavior
Issue number6
StatePublished - Jun 1978
Externally publishedYes


  • Adaptation
  • Cross-tolerance
  • Endorphins
  • Morphine
  • Pain
  • Rats
  • Stress-produced analgesia
  • Tolerance


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