Contrasting effects of acute vs. chronic tricyclic antidepressant treatment on central morphine analgesia

Pain. 1984 Dec;20(4):323-334. doi: 10.1016/0304-3959(84)90110-6.


Antinociception following central opioid microinjection in rats was assessed weekly via a tail-flick procedure during chronic tricyclic antidepressant (TCA) treatment. (1) Daily TCA: Subcutaneous injections of desipramine (DMI), 30 mg/kg, chlorimipramine (CMI), 10 mg/kg, or saline, 1 ml/kg, were given daily for 22 days. Morphine sulfate (M), 5 micrograms, was microinjected into the ventrolateral periaqueductal gray (VLPAG) at 7 day intervals. On day 1, DMI or CMI enhanced M analgesia whereas saline did not. Augmentation of M disappeared by days 8 and 15 for CMI and DMI, respectively, and was replaced by attenuation which was still observed on day 22 for both TCAs. L-Tryptophan (LT), 100 mg/kg, i.p., on days 15 and 22 temporarily restored TCA enhancement of M. Fourteen days after cessation of all daily TCA treatments, enhancement of M by CMI was similar to that observed on day 1, whereas recovery of DMI-induced facilitation was incomplete. (2) Weekly TCA: Weekly treatment with DMI, CMI, or saline in the same doses as above had similar effects. M analgesia was enhanced by the TCAs but not saline on day 1; this facilitation was absent by day 15. Attenuation of M by DMI or CMI was evident on day 22; 2 weeks after cessation of all weekly TCA treatments, complete recovery of TCA-induced augmentation was observed. Loss of M facilitation during chronic daily or weekly TCA administration may be related to reduction of central opioid and/or 5-HT2 receptors.

Publication types

  • Comparative Study

MeSH terms

  • Analgesia*
  • Animals
  • Clomipramine / pharmacology*
  • Desipramine / pharmacology*
  • Male
  • Morphine*
  • Pain / drug therapy
  • Pain / physiopathology*
  • Periaqueductal Gray / drug effects
  • Rats
  • Rats, Inbred Strains
  • Receptors, Opioid / drug effects
  • Receptors, Serotonin / drug effects
  • Time Factors


  • Receptors, Opioid
  • Receptors, Serotonin
  • Morphine
  • Clomipramine
  • Desipramine