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Variation in tolerance to the antinociceptive, hormonal and thermal effects of morphine after a 5-day pre-treatment of male rats with increasing doses of morphine

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Abstract

The manifestation of tolerance to the effects of morphine on nociception and the secretion of anterior pituitary hormones, and the correlation of hormonal effects to changes in body temperature and to hypothalamic monoamines were studied in male rats. Morphine (three times a day in increasing doses) or saline (control) were administered intraperitoneally during a 5-day treatment and either saline or morphine was administered as an acute challenge 92 h later. The influence of the thermal environment on the effect of morphine on the body temperature was also studied.

The 5-day morphine regimen was sufficient for the development of tolerance to the antinociceptive effect of morphine. After a 92-h lag-time, the tolerance was still complete. Tolerance to the depressant effect of morphine (10–25 mg/kg) on cold-stimulated TSH secretion was seen at 2 h, but was only barely detectable at 1 h, after the injection of a challenge dose. On the other hand, a tolerance to the stimulatory effect of morphine on prolactin secretion was already seen 1 h after the acute dose of morphine. Tolerance to the hypothermic effect of morphine (25 mg/kg) was evident in rats kept at +4°C after the challenge dose. On the contrary, no tolerance to the hyperthermic effect of morphine (15 or 25 mg/kg) was observed in rats kept at +30°C. However, the hyperthermia was reversed when these rats were moved to +4°C for 30 min, irrespective of whether they were morphine pretreated or not. Thus the removal of the hyperthermic stimulus decreased the core temperature of all rats.

We conclude, that with a 5-day morphine regimen and a 4-day lag time, tolerance developed to the antinociceptive, hypothermic and some hormonal effects of mor phine but not to its hyperthermic effect or to its effects on hypothalamic 5-HIAA concentrations. Neither the changes in the rectal temperature nor the minor alterations in the concentrations of the hypothalamic amine neurotransmitters correlated with the manifestation of tolerance to the cold-stimulated TSH secretion.

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Author notes

  1. S. A. Borisenko

    Present address: Russian Academy of Medical Sciences, Institute of Pharmacology, Moscow, Russia

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, University of Helsinki, (Siltavuoreupenger 10), SF-00014, P.O. Box 8, Finland

    P. T. Männistö, S. A. Borisenko, P. Rauhala, P. Tuomainen & R. K. Tuominen

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  1. P. T. Männistö
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  2. S. A. Borisenko
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  3. P. Rauhala
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  4. P. Tuomainen
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Correspondence to: P. T. Mannisto at the above address

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Männistö, P.T., Borisenko, S.A., Rauhala, P. et al. Variation in tolerance to the antinociceptive, hormonal and thermal effects of morphine after a 5-day pre-treatment of male rats with increasing doses of morphine. Naunyn-Schmiedeberg's Arch Pharmacol 349, 161–169 (1994). https://doi.org/10.1007/BF00169832

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