Diurnal Variations in Plasma ACTH, Cortisol and Beta-Endorphin Levels in Cocaine Addicts

Abstract

In order to establish possible alterations in the hypothalamic pituitary-adrenal axis and in ACTH-related opioids in cocaine addicts, plasma ACTH, cortisol and β-endorphin levels were measured throughout the day in 9 cocaine addicts [age: 27 ± 5 years (mean ± SE); weight: 72 ± 6.1 kg, duration of cocaine addiction: at least 2 years] on the day of their admission to a recovery community for drug abusers (first test) and after 15 days of abstinence (second test). Nine normal controls (age: 28 + 6 years; weight: 73 ± 3.2 kg) were tested only once in a similar manner. Blood samples were taken at 06.00, 08.00, 10.00, 12.00, 18.00 and 20.00 h and served for hormonal assays. Urine samples were taken from cocaine addicts at 08.00 h on the experimental day and on the following day. Results of both urine assays were positive for cocaine catabolites, indicating cocaine administration during the day before the experimental test. From the day of their admission in the community (1st experimental day), the patients were forbidden to use cocaine. For 4 days after admission, they were treated with symptomatics to attenuate withdrawal symptoms. Thereafter, the patients underwent a washout period of pharmacological treatments for 10 days before being retested (second test). Urine samples taken at 08.00 h on this second experimental day and on the next day were negative for the presence of drug catabolites. During the first test, cocaine addicts showed higher plasma ACTH, cortisol and β-endorphin levels than normal controls at all examined time points. However, maximal and minimal secretory periods and the general temporal structure of all hormonal secretions coincided in the two groups. No significant quantitative or qualitative differences in the secretory pattern of ACTH, cortisol and β-endorphin were observed between normal controls and cocaine addicts as tested after 15 days of abstinence. The results fail to show alterations in the diurnal hormonal secretory rhythms of ACTH, cortisol and β-endorphin in cocaine addicts. The enhancement in the overall ACTH, cortisol and β-endorphin secretions in cocaine addicts during the first, but not the second test, may be supposed to depend on recent cocaine self-administration.

Cocaine-mediated supersensitivity of 5-HT2A receptors in hypothalamic paraventricular nucleus is a withdrawal-induced phenomenon

“…This enhanced response of the HPA axis during withdrawal from chronic cocaine has been reported 24 h to 48 h after the last cocaine injection in rats (Peltier et al, 2001;Zhou et al, 2003). Similar results have been reported in human cocaine addicts (Vescovi et al, 1992;Mendelson et al, 1998).…”

Daily cocaine self-administration under long-access conditions augments restraint-induced increases in plasma corticosterone and impairs glucocorticoid receptor-mediated negative feedback in rats

“…Consistent with this possibility, we observed a significant inverse correlation between basal CORT levels and the magnitude of the CORT response from baseline. Notably, it does not appear that human cocaine addicts experience similar reductions in HPA function, since basal cortisol and/or ACTH levels are reportedly unchanged (Mendelson et al, 1988) or elevated (Vescovi et al, 1992;Buydens-Branchey et al, 2002;Contoreggi et al, 2003) during withdrawal. This disparity between our preclinical findings and the clinical data suggests that either there are subtle differences in the effects of cocaine SA on the HPA axis between rats and humans or that our protocol does not precisely simulate the human condition, thus highlighting that, although the long-access SA approach may be useful for investigating certain aspects of cocaine addiction, it is by no means a complete model.…”

“…With repeated cocaine administration, adaptive changes in the HPA axis emerge and can be observed as disrupted basal HPA function during drug withdrawal in cocaine-dependent individuals (Vescovi et al, 1992;Buydens-Branchey et al, 2002;Contoreggi et al, 2003) and in rats (Sarnyai et al, 1998;Zorilla et al, 2001;Zhou et al, 2003). Less is known about how the response of the HPA axis to stressors is altered as a consequence of prior cocaine use.…”

Persistent Increase in Hypothalamic Arginine Vasopressin Gene Expression During Protracted Withdrawal from Chronic Escalating-Dose Cocaine in Rodents

“…The effects of a single dose of cocaine or of stress on ACTH secretion, however, are significantly lower in cocaine-dependent men than in occasional cocaine users or normal subjects (Mendelson et al, 1998;Brady et al, 2009;Back et al, 2010), showing tolerance as found in the animal model after chronic cocaine administration (Zhou et al, 1996). Higher basal plasma ACTH and cortisol levels have been reported in cocaine addicts 1 day after the cessation of cocaine self-administration (Vescovi et al, 1992). In cocaine addicts with depressive symptoms, basal plasma cortisol levels are increased during early cocaine abstinence (Elman et al, 1999;Buydens-Branchey et al, 2002), an effect that may persist weeks and even months during abstinence (Contoreggi et al, 2003;Wilkins et al, 2005).…”