Morphine Withdrawal Alters Anterior Pituitary Hormone Secretion, Brain Endopeptidase Activity and Brain Monoamine Metabolism in the Rat

Abstract

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 biogenic amines and body weight were studied during abrupt morphine withdrawal. Cold stimulated secretion of thyrotropin and the secretion of growth hormone were both decreased whereas that of prolactin was increased. In the hypothalamus both prolyl endopeptidase and dipeptidyl peptidase IV activities were concomitantly increased. The hypothalamic 5 hydroxyindole acetic acid levels were also increased. Changes in hormone secretion, peptidase activity and monoamine turnover had returned to baseline levels by 92 hr. Our results indicate that morphine withdrawal and the associated stress produce alterations in anterior pituitary thyrotropin and growth hormone secretion. Concomitant increases in hypothalamic prolyl endopeptidase and dipeptidyl peptidase activities may contribute to these changes.

Activities of prolyl endopeptidase and dipeptidyl peptidase IV in brain structures of rats with dopamine deficiency-dependent MPTP-induced depressive syndrome

“…The observed changes are nonspecific for depressive states and reflect the reaction of peptidases in these structures to stress stimulation (repeated administration of drugs). This assumption is confirmed by published data on variations in hypothalamic peptidase activities in stress situation after morphine withdrawal results [8]. In our experiments, changes observed in the hypothalamus were more persistent than those in the nucleus accumbens.…”

Desmopressin accelerates the rate of urinary morphine excretion and attenuates withdrawal symptoms in rats

“…) is consistent with reports indicating that most weight loss occurs 48 h after the final morphine injection in morphine‐dependent animals . Weight loss is a primary factor to consider during early morphine withdrawal in rats, because it is indicative of physical dependence level . Although desmopressin appeared to have had no effect on weight loss in the morphine‐dependent rats examined in the present study, it may have reduced the severity of their morphine withdrawal symptoms.…”

“…The observation of weight loss after discontinuation of morphine (Fig. ) is consistent with reports indicating that most weight loss occurs 48 h after the final morphine injection in morphine‐dependent animals . Weight loss is a primary factor to consider during early morphine withdrawal in rats, because it is indicative of physical dependence level .…”

“…Many studies have indicated that vasopressin is a primary factor in the regulation of anxiety and depression . Among these studies, that of Ishizuka et al ., which examined the effect of a selective serotonin re‐uptake inhibitor (SSRI) and a serotonin‐noradrenaline re‐uptake inhibitor (SNRI), demonstrated that vasopressin V1b receptors are mediators for anti‐anxiety drugs .…”

The effect of opium addiction on thyroid function tests

“…Morphine increases hormones such as adrenalin, noradrenaline, corticosterone and glucagon [17-19] and can reduce the activity of hypothalamic-pituitary axis [20], but in regard to alterations of T3, T4 and especially TSH levels following morphine consumption, different and sometimes controversial results have been reported [20,21]. Some researchers have reported decrease of TSH level but no alterations in T3 and T4 levels during morphine consumption [20], while some others have reported decrease of TSH, T3 and T4 levels following short-term consumption of morphine [22].…”