MORPHINE-WITHDRAWAL ALTERS ANTERIOR-PITUITARY HORMONE-SECRETION, BRAIN ENDOPEPTIDASE ACTIVITY AND BRAIN MONOAMINE METABOLISM IN THE RAT

Rats were made tolerant to morphine by a 5-day regimen with increasing doses. The time course of changes in serum anterior pituitary hormone levels, brain endo- and exopeptidase activity, levels of brain biogen ic amines and body weight were studied during abrupt morphine withdraw al. Cold stimulated secretion of thyrotropin and the secretion of grow th hormone were both decreased whereas that of prolactin was increased . In the hypothalamus both prolyl endopeptidase and dipeptidyl peptida se IV activities were concomitantly increased. The hypothalamic 5 hydr oxyindole acetic acid levels were also increased. Changes in hormone s ecretion, peptidase activity and monoamine turnover had returned to ba seline levels by 92 hr. Our results indicate that morphine withdrawal and the associated stress produce alterations in anterior pituitary th yrotropin and growth hormone secretion. Concomitant increases in hypot halamic prolyl endopeptidase and dipeptidyl peptidase activities may c ontribute to these changes.