Effect of chronic morphine treatment on thyrotropin and prolactin levels and acute hormone responses in the rat

P Rauhala, PT Mannisto and RK Tuominen

Department of Pharmacology and Toxicology, University of Helsinki, Finland.

The effects of three chronic morphine regimens on basal and cold- stimulated thyrotropin (TSH) and on prolactin levels were studied in male rats with and without acute morphine challenge. All the chronic regimens decreased basal and cold-stimulated TSH levels, but only one regimen (10 mg/kg b.i.d.) significantly enhanced the prolactin levels. The altered cold-stimulated TSH and prolactin levels were recovered within about 96 and 48 hr, respectively, after the last morphine injection on the 7-day pretreatment period. After the chronic administration (14 days), acute morphine challenges were performed either when cold-stimulated TSH secretion was suppressed (12- and 24-hr lag time) or when the response to cold was normalized (96-hr lag time). When the TSH levels were still low, the small challenge doses of morphine (10 and 15 mg/kg) no longer suppressed the TSH secretion. This was due neither to the real tolerance nor to the persistent effect of chronic morphine but to the withdrawal stress, which was also reflected as elevated corticosterone levels. However, after a 96-hr lag time, the challenge doses of morphine decreased TSH secretion after each morphine regimen as effectively as in the naive rats. Thus, the regimens did not induce the development of tolerance to the effect of morphine on cold- stimulated TSH secretion. Most regimens seemed to cause some tolerance to the stimulatory effect of morphine on prolactin secretion irrespective of the duration of the lag time. Even after the mildest regimen (10 mg/kg once a day), a tolerance developed to the antinociceptive effect of morphine, and it lasted well up to 96 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 246, Issue 2, pp. 649-654, 08/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics