Impaired circadian rhythmicity of β-lipotrophin, β-endorphin and ACTH in heroin addicts

Abstract

The circadian rhythm of plasma proopiocortin-related peptides was studied in 15 heroin addicts and in 6 sex-and age-matched controls. ACTH, \g=b\-l i potrophin, (\g=b\-LPH), \g=b\-endorphin(\g=b\-EP) and cortisol were measured by RIA either directly (cortisol), or after plasma extraction (ACTH) and Sephadex G-75 gel chromatography (\g=b\-LPH and \g=b\-EP) every 4 h from 8 a.m. to 8 p.m. and again at 8 a. m. the next morning.The means of the two 8 a.m. measurements of \g=b\-LPH (2.67 \ m=+-\ 0.34 fmol/ml, mean \ m=+-\ SE), ACTH (2.74 \ m=+-\ 0.71) and cortisol (218 \ m=+-\ 31 pmol/ml) levels in heroin addicts were significantly lower than those in controls (6.28 \ m=+-\ 0.61, 10.1 \ m=+-\ 0.74 and 364 \ m=+-\ 27, respectively, P < 0.01) while \g=b\-EP concentrations in heroin addicts (5.1 \ m=+-\ 0.6) were similar to those of healthy volunteers (6.44 \m=+-\ 0.56).In controls, all three peptides and cortisol show a circadian rhythm of secretion, the lowest values being in the evening and the highest ones in the morning. Heroin addicts partially lack this phenomenon showing constant levels of the three proopiocortin-related peptides throughout the day, with a slight but significant decrease of plasma cortisol. In the 7 subjects who took heroin throughout the study, no systematic changes were observed in the three proopiocortin-related peptides, while it seems that this group of addicts shows a cortisol decrease in the evening to a lesser extent than subjects receiving methadone maintenance only.These data show a decreased basal \g=b\-LPH, ACTH and cortisol secretion in heroin addicts, despite normal \g=b\-EP levels. This would indicate that anterior pituitary proopiocortin synthesis and/or secretion is affected in these subjects, and that there is also some impairment in the structures controlling the circadian rhythmicity of ACTH and related peptides.Partly supported by CNR grant 82.02145.04 and CNR PF 'MPR' SP 7.Since the discovery of opiate receptors in human brain, a great deal of attention has been paid to the possible relationship between their natural ligands, the endogenous opioid peptides and the onset of morphine or heroin addiction. In this context, it has been proposed that a genetic deficiency of endogenous opioid peptides may be a cause of drug-seeking behaviour (Goldstein 1978), as has also been suggested for alcohol abuse (Blum 1980). The link between exogenous and endogenous opioids is supported by the observation that chro¬ nic morphine treatment causes a decrease in the ß-endorphin-like immunoactivity (ß-ELI) content of the anterior and intermediate posterior pituitarylobes of rats (Volker et al. 1978) while plasma concentrations of these substances were found to be depressed in heroin addicts (Ho et al. 1980). However, the antisera employed in the above stud¬ ies recognize all the peptides or fragments con¬ tained in the C-terminal portion of ß-lipotrophin (ß-LPH), so even though the results are suggestive, they do not establish which of the peptides whithin the endorphin family are depressed in...

Gonadal and Adrenal Abnormalities in Drug Users: Cause or Consequence of Drug Use Behavior and Poor Health Outcomes

“…Opiate administration disrupts this pathway through the inhibition of CRH release, leading to reduced cortisol production [19] . Consistent with this observation, small studies have shown a high prevalence of adrenal insufficiency in opiate dependent subjects, with a high prevalence of abnormal ACTH stimulation tests [20] , low cortisol concentrations accompanied by low ACTH levels and atypical circadian production of these hormones [21] . In addition, the administration of metyrapone, a cortisol synthesis inhibitor used to test the integrity of the HPA axis, shows decreased HPA activation in heroin users [22] .…”

Serum Cortisol Secretion During Heroin Abstinence Is Elevated Only Nocturnally

“…Indeed, the widespread distributions of these receptors confirm the broad brain effects of the HPA response to psychological stress (4). administered with significantly lower cortisol levels than controls (1,(6)(7)(8). In non-heroinusing individuals, hypocortisolism is observed after administration of codeine or the metenkephalin analog FK 33-824 (9,10).…”

Plasma Beta-Endorphin in Response to Oral Glucose Tolerance Test in Obese Patients

“…In view of the fact that endogenous opioids are involved in compulsive behavior such as alcoholism {Genazzani, Naffi, Facchinetti, Mazzella, Perrini, Sinforiani, Petraglia and Savoldi 1982) and heroin addiction {Facchinetti, Gasso, Petraglia, Perrini, Volpe and Genazzani 1984) and that increases of B-Ep are associated with mood disturbances {Brambilla, Genazzani, Facchinetti, Perrini, Petraglia, Sacchetti, Scarone, Guatello and D'Antria 1981) we believe that raised B-Ep levels in obese patients could participate to bulimia and hyperphagia typical of the disease.…”