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A series of experiments was conducted in adult male rats to study the development of tolerance to and dependence on morphine in the neural processes controlling LH and prolactin secretion. The central mechanisms controlling both these hormones became tolerant following chronic application of the opiate agonist; this was seen in the form of diminished responsiveness to the agonist with time. There was an apparently greater degree of tolerance in the mechanisms regulating LH secretion than in those regulating prolactin secretion.

In parallel experiments, the opiate antagonist naloxone was used to test for the development of dependence in rats chronically treated with morphine. While behavioural signs of physical dependence (withdrawal) were evident, the LH and prolactin responses proved to be the same as those observed in response to acute administration of opiate agonists (i.e. naloxone respectively decreased and increased serum LH and prolactin concentrations in animals chronically treated with morphine). This paper may represent the first report of such paradoxical responses to naloxone. It also demonstrates that opioid tolerance and dependence may exist as two separate phenomena in vivo.

J. Endocr. (1986) 108, 181–189