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Role of brain catecholamines and 5-hydroxytryptamine in morphine induced temperature changes in normal and tolerant rats and mice

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Summary

Morphine (5–20 mg/kg) produced hyperthermia in normal, unrestrained rats. Rats which were chronically treated with morphine became tolerant and physically dependent but did not develop tolerance to the acute hyperthermia. Pretreatment of rats with 6-hydroxydopamine to deplete brain catecholamines potentiated the acute morphine hyperthermia in normal rats but not in tolerant rats. The effect is probably related to brain dopamine. Depletion of brain 5-hydroxytryptamine (5-HT) produced by 5,6-dihydroxytryptamine pretreatment, antagonized the acute morphine hyperthermia in both normal and tolerant rats. Morphine (5–20 mg/kg) produced hypothermia in both normal and morphine tolerant mice. Pretreatment of normal mice with 6-hydroxydopamine depleted brain noradrenaline and dopamine and antagonized the hypothermia. Pretreatment with pargyline and 6-hydroxydopamine caused a greater loss of cerebral dopamine than 6-hydroxydopamine alone and resulted in an acute morphine hyperthermia. Morphine also caused hyperthermia when given to tolerant mice pretreated with 6-hydroxydopamine. Pretreatment of normal mice with 5,6-dihydroxytryptamine totally abolished the acute morphine hypothermia. In tolerant mice treated with 5,6-dihydroxytryptamine morphine caused a rise in temperature. It is concluded that (1) a single dose of morphine given to normal rats shifts a hypothalamic 5-HT: dopamine balance in favour of 5-HT; (2) activation of a 5-HT mechanism causes hyperthermia whereas dopamine mediates hypothermia; (3) rats chronically treated with morphine do not become tolerant to the acute hyperthermia because morphine tolerance has little effect on 5-HT; (4) brain dopamine mechanisms readily develop tolerance to morphine; (5) the hypothermia produced by a single dose of morphine in normal mice is mediated by dopamine and, to a lesser extent, 5-HT mechanisms; (6) the hypothermic mechanisms rapidly develop tolerance to morphine; (7) loss of cerebral dopamine and 5-HT in morphine tolerant mice leads to an acute morphine hyperthermia due to another neurotransmitter.

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  1. Department of Physiology, The Medical School, University of Manchester, M13 9PT, Manchester, UK

    P. Slater & C. Blundell

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  1. P. Slater
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  2. C. Blundell
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Slater, P., Blundell, C. Role of brain catecholamines and 5-hydroxytryptamine in morphine induced temperature changes in normal and tolerant rats and mice. Naunyn-Schmiedeberg's Arch. Pharmacol. 313, 125–130 (1980). https://doi.org/10.1007/BF00498567

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  • DOI: https://doi.org/10.1007/BF00498567

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