Contrasting effects of acute vs. chronic tricyclic antidepressant treatment on central morphine analgesia.
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.
D000698:Analgesia; D000818:Animals; D002997:Clomipramine / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology*; D008297:Male; D009020:Morphine; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D010487:Periaqueductal Gray / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D013997:Time Factors
D011957:Receptors, Opioid; D011985:Receptors, Serotonin; D009020:Morphine; D002997:Clomipramine; D003891:Desipramine