Chronic exposure to morphine and naltrexone induces changes in catecholaminergic neurotransmission in rat brain without altering μ-opioid receptor sensitivity

Taco J. De Vries, Guno H K Tjon Tien Ril, Jan Willem Van der Laan, Arie H. Mulder, Anton N M Schoffelmeer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


In order to investigate the role of μ-opioid receptor regulation in catecholaminergic neurotransmission during morphine tolerance/dependence and supersensitivity, we measured changes in number and functional properties of two distinct types of μ receptors in the brain of rats chronically treated with morphine and naltrexone. In membranes of striatum and cortex of morphine treated rats the binding of μ ligand [3H]DAMGO was unaltered, whereas an increase in μ binding sites was found in these brain regions of naltrexone treated rats. The ability of the μ agonist DAMGO to inhibit the dopamine D-1 receptor stimulated cAMP production in striatal slices and the electrically evoked release of [3H]noradrenaline from cortical slices was unaffected in both experimental groups. The major changes found were an increased D-1 receptor stimulated cAMP production and an enhanced release of nonadrenaline in morphine treated rats and a decreased D-1 receptor stimulated cAMP production in naltrexone treated rats. These data support the hypothesis that tolerance and supersensitivity to morphine and other μ-opioids may be caused by up- and down-regulated neuronal second messenger systems linked to μ-opioid receptors, rather than by changes in the sensitivity of the μ-opioid receptor itself.

Original languageEnglish
Pages (from-to)1685-1693
Number of pages9
JournalLife Sciences
Issue number21
Publication statusPublished - 1 Jan 1993

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