Beta-endorphin Research Articles

Male Violence, Stress, and Neuroendocrine Parameters in Pregnancy: A Pilot Study

Stress during pregnancy has been associated with a number of adverse outcomes. This study compared and correlated neuroendocrine parameters in women (n=8) who self-reported battering during their pregnancy to those in women who did not (n=8). Women who identified themselves as having a violent relationship with an intimate partner were recruited from a rural midwestern community. They were matched on age, self-reported ethnicity, parity, gestational age, and personal and family income with nonbattered controls. Midgestational measures of self-reported stress levels showed that battered women reported markedly higher levels of anxiety and depression. Neuroendocrine levels were not different between groups (battered vs. nonbattered); however, the relationships among hormones were different between groups. In nonbattered women, adrenocorticotropic hormone (ACTH) and cortisol levels were correlated but not in battered women. Beta endorphin and ACTH levels in battered women showed a significant linear relationship but not in nonbattered women. These results suggest that the maternal experience of stress alters the relationship of hypothalamic-pituitary-adrenal-placental axis hormones despite the lack of absolute differences in blood levels.

The Diminution of Beta-Endorphin in Blood Plasma by the Effect of Semen Emission is Less Common in Men With Idiopathic Severe Oligoasthenozoospermia Than in Fertile Men

To compare the beta-endorphin (BE) blood plasma concentration among men with idiopathic severe oligoasthenozoospermia (OA) and fertile men before and after the effect of semen emission, and the concentration of BE in seminal plasma among both groups.

Multi-factor analysis of umbilical plasma β-endorphin levels in neonates

目的 研究不同妊娠、分娩因素对脐血β内啡肽(β-EP)水平的影响.方法收集不同孕期的新生儿脐血共95例,用放射免疫法测定其β-EP水平,以β-EP为因变量,以新生儿胎龄、性别、出生体重、分娩方式、母患高血压、母患糖尿病、宫内窘迫、胎膜早破为自变量,进行多元线性逐步回归,筛选出可能的影响因素,进一步研究不同影响因素时脐血β-EP变化.结果胎龄、分娩方式、宫内窘迫是影响脐血β-EP水平的重要因素(P均＜0.05).早产儿组脐血β-EP值高于足月儿组,分别为(409.5±150.1)pg/ml、(261.4±141.5)pg/ml,差异均有统计学意义(P均＜0.05).阴道分娩组及产钳助产组高于选择性剖宫产组,差异有统计学意义(P均＜0.05).阴道分娩组与产钳助产组比较,差异无统计学意义(P均＞0.05).宫内窘迫组高于无宫内窘迫组,差异有统计学意义(P均＜0.01).结论分娩应激、疼痛会使β-EP升高,缺氧是影响β-EP水平的一个重要因素,脐血β-EP水平可作为胎儿缺氧的一个指标.早产儿脐血β-EP高于足月儿是否是早产儿易发生呼吸暂停的病理生理基础,有待进一步研究。

Determination of beta-endorphin in hypothalamus of rat with primary trigeminal neuralgia

To determine the level and the role of beta-endorphin in hypothalamus of rat with trigeminal neuralgia. The animal model of primary trigeminal neuralgia in rat was established, the contents of beta-endorphin were measured by radioimmunoassay techniques. The beta-endorphin of hypothalamus in experimental group was significantly lower than other groups (P < 0.01). Beta-endorphin may play important roles in primary trigeminal neuralgia.

Effects of subcutaneous administration of daidzein on blastocyst implantation in rats

The study was conducted to investigate the effects of phytoestrogen daidzein on blastocyst implantation in rats. Following successful mating, female rats were given daidzein by subcutaneous administration at the dose of 0 (vehicle control, n = 15), 50 mg/kg body weight ( n = 15) and 150 mg/kg body weight ( n = 15) daily on day 1–7 of pregnancy and were sacrificed on day 8 of gestation. The results revealed that high-dose treatment (150 mg/kg body weight) significantly diminished the rate of blastocyst implantation and serum levels of gonadotropin-releasing hormone (GnRH), progesterone, and gonadotropins (FSH and LH), meanwhile the serum level of beta endorphin increased significantly. These effects were not observed in the low-dose treatment group (50 mg/kg body weight). The results of this study suggested that the anti-implantation effects of daidzein are probably caused by the interference of the hypothalamus-pituitary-gonadal axis which is involved in the implantation process.

Plasma Beta-Endorphin Levels Before and After Relief of Cancer Pain

Plasma Beta endorphin (BE) is an endogenous peptide opioid derived form pro-opiomelanocortin. Although the role of plasma BE in pain regulation is unclear, plasma BE levels have been reported to correlate inversely with pain levels in cancer pain. To measure BE levels in patients with cancer before and after pain relief with different analgesic modalities, to evaluate the relationship between cancer pain, pain control and plasma BE levels. Prospective interventional study conducted in a university hospital setting. Patients with intractable pain due to upper abdominal visceral malignancies (pancreatic, liver and gastric cancers) agreed to participate in the study. Pain relief was provided with one of four primary modalities: 1) oral continuous release morphine, 2) thoracic epidural morphine boluses, 3) alcohol celiac plexus blocks or 4) interpleural infusions of bupivacaine. Blood samples for plasma BE levels were taken before treatment and at the time of maximal pain relief obtained with the particular treatment modality. Pain levels were determined using a 10 cm visual analogue scale. BE levels were measured by competitive radioimmunoassay using 125I Beta endorphin. Average pain scores decreased from 7.3 +/- 1.27 (SD) before treatment to 1.2 +/- 1.18 (SD) after treatment (p<0.0001). Satisfactory pain relief was obtained with each of the four treatment modalities and was associated with a significant increase in plasma Beta levels. The mean plasma BE level for all groups before treatment was 18.9 +/- 5.4 pg/ ml (range 2.0 to 29.6 pg/ml) compared to 38.7 +/- 17.6 pg/ml (range 13.2 to 67.9 pg/ml) after pain relief (p < 0.0001). Plasma BE levels increased with improved pain control with each of the four analgesic modalities, including oral and epidural morphine. Plasma BE levels increased with improved pain control in patients with upper abdominal gastrointestinal malignancies. Although the role of plasma BE in pain pathophysiology is unclear, it appears that pain relief per se, and not the analgesic technique, modulates plasma BE levels. This suggests that plasma BE levels may serve as an objective measure of cancer pain severity and corroborate the patient's report of pain relief.

Biochemical Comparison between Radon Effects and Thermal Effects on Humans in Radon Hot Spring Therapy

The radioactive and thermal effects of radon hot spring were biochemically compared under a sauna room or hot spring conditions with a similar chemical component, using the parameters that are closely involved in the clinic for radon therapy. The results showed that the radon and thermal therapy enhanced the antioxidation functions, such as the activities of superoxide dismutase (SOD) and catalase, which inhibit lipid peroxidation and total cholesterol produced in the body. Moreover the therapy enhanced concanavalin A (ConA)-induced mitogen response and increased the percentage of CD4 positive cells, which is the marker of helper T cells, and decreased the percentage of CD8 positive cells, which is the common marker of killer T cells and suppressor T cells, in the white blood cell differentiation antigen (CD8/CD4) assay. Furthermore, the therapy increased the levels of alpha atrial natriuretic polypeptide (alpha ANP), beta endorphin, adrenocorticotropic hormone (ACTH), insulin and glucose-6-phosphate dehydrogenase (G-6-PDH), and it decreased the vasopression level. The results were on the whole larger in the radon group than in the thermal group. The findings suggest that radon therapy contributes more to the prevention of life-style-related diseases related to peroxidation reactions and immune suppression than to thermal therapy. Moreover, these indicate what may be a part of the mechanism for the alleviation of hypertension, osteoarthritis (pain), and diabetes mellitus brought about more by radon therapy than by thermal therapy.

Effects of morphine and time of day on pain and beta-endorphin.

Clients report more pain at some times of day than at others due, in part, to the temporal variation of the body's inhibitory pain response. The analgesic effectiveness of morphine varies with the time of day, perhaps due to the inhibiting or enhancing effects of the drug on plasma beta-endorphin (BE). This experiment was designed to examine the timed effects of morphine on the pain-induced BE response. Six groups of treatment mice (injected with morphine sulfate) and 6 groups of control mice (injected with saline) were exposed to an acute pain stimulus at 4-h intervals, and blood was collected. Plasma BE was analyzed using radioimmunoassay. Control mice showed a robust circadian BE-response rhythm with a peak at 0000 and a nadir at 1200, whereas the BE response of mice that received morphine was arrhythmic. Animals that received morphine tolerated the noxious stimulus longer, but the analgesia varied with time of day. These results indicate that morphine abolishes the rhythmic BE response to pain and does not inhibit pain equally at all times of day. Morphine doses should be titrated to maximize the endogenous pain control system while achieving analgesia with decreased dosages.

The role of GabaA receptors in the neural systems of the ventromedial hypothalamus-nucleus infundibular region in the control of GnRH release in ewes during follicular phase.

To examine the role of the GABAA receptor mediating systems in the control of gonadotropin releasing hormone (GnRH) release from the ventromedial-infundibular region (VEN/NI) of the hypothalamus of ewes during the follicular phase of the estrous cycle, the extracellular concentrations of GnRH, beta-endorphin (B-END), noradrenaline (NE), dopamine (DA), and their metabolites MHPG, DOPAC and concentration of luteinizing hormone (LH) in blood plasma were quantified during local stimulation or blockade of GABAA receptors with muscimol and bicuculline, respectively. Stimulation of GABAA receptors attenuated GnRH and LH release, increased beta-endorphin outflow and dopaminergic activity but had no evident effect on noradrenergic activity. Blockade of GABAA receptors decreased beta-endorphin release but had no evident effect on the extracellular concentration of GnRH, LH levels in the blood and catecholaminergic activity. It is suggested that suppression of GnRH/LH release under muscimol treatment may result from activation of GABAA receptors on GnRH nerve terminals and through GABAA receptor mechanism activated beta-endorphinergic and dopaminergic neurons in the VEN/NI. Lack of changes in NE and MHPG concentration during stimulation or blockade of GABAA receptors suggests, that during the follicular phase of the estrous cycle the noradrenergic system in the VEN/NI is not involved in the control of GnRH/LH release by GABA.

Endogenous opioids and epinephrine in nitroglycerin provocation tilt test in patients with neurally mediated syncope.

Endogenous opioids and catecholamines are involved in autonomic activity. Nitroglycerin provocation tilt is a useful modality for evaluating neurally mediated syncope. Endogenous opioids and epinephrine might play an important role in nitroglycerin provocation tilt. To investigate whether or not opioids and catecholamines are involved in the pathogenesis of nitroglycerin provocation tilt, we measured the temporal changes of the plasma levels of beta endorphin, norepinephrine, and epinephrine in 64 patients with syncope of unknown etiology, and compared the findings with those of 16 patients who underwent isoproterenol provocation tilt (1-3 microg/min) test with a positive response. We performed a 20 minute control tilt (80 degrees) followed by a nitroglycerin provocation tilt of 20 minutes with the intravenous infusion of nitroglycerin. Nitroglycerin infusion was started at 250 microg/h, and was increased by 250 microg/h every 3 minutes up to 1500 microg/h during the tilt test. Beta-endorphin, norepinephrine, and epinephrine were measured in peripheral venous blood in the supine position 2, 10, and 20 minutes after the start of the tilt test, and also at the onset of syncope. Twenty-six patients had a positive response to the control tilt (group 1), and 22 patients had a positive response to nitroglycerin provocation tilt (group 2). The remaining 16 patients had a negative response to both control tilt and nitroglycerin provocation tilt (group 3), compared with isoproterenol provocation tilt patients (group 4). Beta-endorphin and epinephrine only significantly increased in groups 1 and 2 (beta-endorphin; from 7.3 +/- 3.3 pg/mL to 19.9 +/- 17.7 pg/mL, in group 1, P < 0.05; from 7.3 +/- 2.9 to 16.5 +/- 10.7 pg/mL, in group 2, P < 0.05; epinephrine; from 42 +/- 58 pg/mL to 157 +/- 161 pg/mL, in group 1, P < 0.05: from 33 +/- 25 to 202 +/- 252 pg/mL, in group 2, P < 0.05), but not in groups 3 and 4. Beta-endorphin and epinephrine might participate in the pathophysiology in conventional tilt-induced as well as nitroglycerin provocation tilt-induced syncope in patients with neurally mediated syncope.

No Effect of a Selective Serotonergic/Noradrenergic Reuptake Inhibitor on Endurance Performance

The purpose of the present study was to examine the effects of a selective serotonin/noradrenaline (5-HT/NA) reuptake inhibitor (SNRI) on exercise performance. Seven well-trained male cyclists completed 2 time trials in a doubleblind randomized crossover design ingesting either placebo (PLAC) or 2 × 37.5 mg of Venlafaxine (VEN). Blood samples were collected for adrenocorticotropin hormone (ACTH), prolactin (PRL), cortisol, growth hormone (GH), beta-endorphins, and catecholamines and were taken at rest, at 30-min time intervals, at the end of exercise, and during recovery. Performance was not influenced by the SNRI (VEN: 92 min ± 3 min, PLAC: 92 min ± 1 min). Lactate concentrations, heart rate, and fatigue scores were not different between trials. All hormones increased during exercise in both trials. In the VEN trial, ACTH, beta endorphins, and NA concentrations were higher. The results from the present study demonstrate that a SNRI is not able to affect endurance performance in well-trained cyclists. However, it seems as though the hormonal response to the combination of the pharmacological manipulation and exercise is regulated more by the noradrenergic drive.

Anaesthesia for fetal surgery.

*Department of Anesthesia, Children’s Hospital, Harvard Medical School, Boston, MA,**Department of Anesthesiology and Critical Care, The Children’s Hospital of Philadelphia,University of Pennsylvania School of Medicine, Philadelphia and †Department of Anesthesia andCritical Care, The Hospital of the University of Pennsylvania, University of Pennsylvania Schoolof Medicine, Philadelphia, PA, USA

Conformational changes in beta-endorphin as studied by electrospray ionization mass spectrometry.

Because of a wide range of physiological functions, the structure of beta-endorphin (BE) is of great interest. In this study, conformational changes in BE induced by methanol are explored with electrospray ionization-mass spectrometry (ESI-MS). Differences in the charge-state distribution (CSD) and the extent of hydrogen/deuterium (H/D) exchange were used to monitor the conformational changes. The latter experiments were conducted via time-resolved ESI-MS in a continuous-flow apparatus. Both these techniques demonstrate that BE exists in a random coil open structure in aqueous media, but it acquires a more compact conformation with increased concentration of methanol. The H/D exchange experiments reveal that BE forms 61% alpha-helix in mixed solvents.

Cardiorespiratory and endocrine effects of endogenous opioid antagonism by naloxone in ponies anaesthetised with halothane

Halothane depresses cardiorespiratory function and activates the pituitary–adrenal axis, increasing beta endorphin. In horses, β endorphin may enhance the anaesthetic-associated cardiorespiratory depression and mortality risk. The authors studied endogenous opioid effects on cardiorespiratory function and pituitary–adrenal activity in halothane-anaesthetised ponies by investigating opioid antagonism by naloxone. Six ponies were anaesthetised three times (crossover design). Anaesthesia was induced with thiopentone and maintained with 1·2 per cent halothane for 2 hours. Immediately after induction, naloxone was administered either intravenously (0·5 mg kg–1bolus then 0·25 mg kg–1hour–1for 2 hours) or intrathecally (0·5 mg) or was replaced by saline as control. Pulse and respiratory rates, arterial blood gases, cardiac output and plasma cortisol and adrenocorticotrophic hormone (ACTH) concentrations were measured. All groups developed cardiorespiratory depression (40 per cent decrease in cardiac output) and plasma cortisol increased. Plasma ACTH concentration was higher in ponies treated with intrathecal naloxone. Endogenous opioids may inhibit ACTH secretion, attenuating the stress response to halothane anaesthesia in equidae.

Role of beta-endorphin in the modulation of immune responses: perspectives in autoimmune diseases.

Until a decade ago, the opioid peptide beta-endorphin (BE) was considered a “neuropeptide”, due to its multiple activities as neurotransmitter and neuromodulator. It is produced as a larger precursor molecule, proopiomelanocortin (POMC), and the POMC precursor molecule is post-translationally processed by a series of enzymatic events, which give rise to a number of peptide hormones e.g. ACTH, and BE. In the CNS, BE is synthesized mainly in the arcuate nucleus of the hypothalamus, and projects in several brain areas. In the periphery the main source of BE is the intermediate pituitary or its vestige (1). Also it was shown that BE is constitutively synthesized by cells of the immune system, that, upon appropriate stimulation release the opioid peptide (2). The hypothalamic peptide CRH, which is considered the main signal for BE synthesis and release in the brain and in the pituitary, can also induce the synthesis and the secretion of the POMC-derived peptides from Peripheral Blood Mononuclear cells (PBMC) and splenocytes (2,3). Consistently, during stress, which is associated with CRH synthesis and secretion, an increase of immunocyte beta-endorphin is present (4). Our laboratory also demonstrated that BE is similarly controlled in lymphocytes and brain by the same neurotransmitters, in fact BE is under a dopaminergic and GABAergic inhibitory tonic control, and a serotoninergic tonic stimulatory input (5,6). Besides hypothalamic releasing hormones and neurotransmitters, also the cytokine 1L-1 has been shown to stimulate BE synthesis and secretion ( 2,3). Beta-endorphin synthesis is therefore subject to many regulatory inputs, coming from both the CNS and the immune system.

Function and regulation of cholecystokinin octapeptide, beta-endorphin and gastrin in anorexic infantile rats treated with ErBao Granules.

To study the role of cholecystokinin octapeptide (CCK-8),beta endorphin (beta EP), and gastrin in an anorexic infantile rat model and no subsequent regulation of nose peptides by the Yunpi complex prescription ErBao Granule. We fed infantile rats with special prepared forage. A liquid extract of ErBao Granule was administered to the rats daily for 3 weeks, CCK-8, beta-EP, and gastrin concentrations in hypothalamus, gastric antrum, and plasma of the rats were measured by radioimmunoassay, and were compared with controls. Treatment of rats with ErBao Granule inhibited CCK-8 secretion and increased beta-EP and gastrin secretion. CCK-8 concentration in hypothalamus and plasma of model control group increased significantly and correlated negatively with food intake of models, respectively. beta-EP concentration in gastric antrum and plasma of model control group decreased significantly and showed a positive correlation with food intake of models, respectively. Hypothalamus concentration of beta-EP was similar in models and controls. Gastrin concentration in gastric antrum of models was lower than in the blank control group, and correlated positively to food intake of models. Finally, CCK-8 concentrations in plasma of rats showed a positive correlation with plasma beta-EP (r=-0.68, P<0.05). The increased plasma and hypothalamus concentration of CCK-8, decreased gastric antrum and plasma level of beta-EP, and decreased gastric antrum concentration of gastrin are associated significantly with the anorexia of infantile anorexic rat models produced by special for-age. ErBao Granule can reverse these changes, which may be the major mechanisms of ErBao Granule simulating feeding.

Neuropéptidos en los núcleos del rafe: estudio inmunocitoquímico

The raphe nuclei are involved in numerous mechanisms, included the antinociceptives. In the raphe nuclei of the cat, the distribution of neuropeptides is not very studied. Aim. To know the distribution of peptidergic fibers and cell bodies in the raphe nuclei of the cat. We studied a total of fifteen neuropeptides. We used four control cats (without colchicine) and six with colchicine (administered into the Sylvian aqueduct). We used an indirect immunocytochemical technique. The histologic controls carried out confirm the specificity of the primary and secondary antibodies used. We observed in the fibers and/or the cell bodies located in the dorsal raphe nucleus a total of 14 neuropeptides, 12 in the raphe pallidus, 11 in the medial raphe, 10 in the raphe magnus, 8 in the raphe pontis and 7 in the raphe obscurus. We observed immunoreactive cell bodies in the raphe pallidus (with neurokinin A/leucine enkephalin), in the medial raphe (beta endorphin/alpha neo endorphin), in the raphe magnus (leucine enkephalin) and in the dorsal raphe (beta endorphin/alpha neo endorphin/methionine enkephalin Arg6 Gly7 Leu8/leucine enkephalin/neurokinin A/neurotensin). 1. There are differences on the distribution of the peptidergic fibers/cell bodies observed in the raphe nuclei of the rat, the cat and the man; 2. The raphe nuclei could receive peptidergic afferences containing dynorphin A, galanin, neuropeptide Y, somatostatin ; 3. The cell bodies located in the medial raphe and containing beta endorphin or alpha neo endorphin could be projecting neurons; 4. There is a great functional complexity in the raphe nuclei due to the great number of neuropeptides observed in them; 5. The neuropeptides could interact between them, and 6. The neuropeptides located in the raphe nuclei could be involved in the control of the nociceptive information.

Dynamic exercise discloses different time-related responses in stress hormones.

Responses to stressful events are generally regarded as reactions of the organism to accommodate to or compensate for stress. This reaction is classically described as an activation of the sympathoadrenal system and the hypothalamic-pituitary-adrenocortical (HPA) axis. Activation of the release of growth hormone and prolactin in blood also occurs during various types of stress. Assuming that the stress response is a neuroendocrine mechanism that occurs in anticipation of physical exercise, we investigated whether an incremental exercise protocol can be used as a model stressor to disclose a distinct pattern of activation in these hormonal systems, which would support the notion that these systems have different roles in preparing the organism for physical activity and recovery. Moreover, such a model may help improve our understanding of the endocrine expressions of psychological stress. After an overnight fast, 8 healthy men (age, 19-26 years) cycled at 40, 60, 80, and 100% of the power output at VO2max in successive time blocks of 10 minutes each up to exhaustion. Venous blood was sampled immediately before exercise, at the end of each block, and during the recovery phase 5 and 30 minutes after exercise. Plasma adrenalin and noradrenalin were measured by high-performance liquid chromatography; plasma adrenocorticotropic hormone, beta-endorphin, cortisol, growth hormone, and prolactin were measured by specific immunoassays. Heart rate and levels of blood lactate and adrenalin were measured as markers of workload-related responses. Results showed that increases in heart rate, lactate, adrenalin, noradrenalin, and growth hormone reflected the relative workload, in contrast to increases in adrenocorticotropic hormone, beta endorphin, and prolactin, which were observed only after exercise reached an intensity of 80% VO2max. Increases in cortisol were found just after exhaustion. The delayed response of cortisol may be initiated by a drop in blood glucose levels but may also be considered preparatory to vigorous muscular effort and protective against tissue damage. Measurement of the cumulative response to exercise shows that activation of stress hormones occurs at different time points, supporting the notion that these hormones have different roles in preparing the organism for physical activity and recovery: ie, workload- and effort-related adaptation on one hand and protection against disturbed homeostasis on the other. The delayed response of the HPA axis during incremental exercise contrasts with the nondelayed HPA axis response observed during psychological stress and points to involvement of different neurobiological and cognitive emotional mechanisms.

β-Endorphin Concentrations in Peripheral Blood Mononuclear Cells of Patients With Multiple Sclerosis

It has been reported that the opioid peptide beta-endorphin (BE) has immunosuppressive effects. Interferon beta (IFN-beta) is a well-established therapy for multiple sclerosis (MS), but immunological mechanisms underlying its beneficial effects in MS are partially undefined. To determine BE levels in peripheral blood mononuclear cells (PBMCs) of patients with relapsing-remitting MS during different phases of disease activity and the possible modulating effects of IFN-beta treatment on PBMC BE synthesis in patients with MS. We measured BE levels in blood samples collected from 6 patients with MS who had not experienced clinical changes during the previous 3 months (patients with stable MS) and from 7 patients with MS during a clinical relapse. We also surveyed BE levels in PBMC samples from 8 patients with MS before treatment and for 6 months after the beginning of IFN-beta administration. The control group was 13 healthy subjects. Low PBMC BE levels were detected in patients with stable MS and in those entering IFN-beta treatment compared with control subjects. Increased BE concentrations were observed in MS patients experiencing a clinical relapse compared with patients with stable MS. During IFN-beta treatment, the levels of BE in PBMC samples from patients with MS increased significantly (after 1 month, P =.02; after 3 months, P =.007; and after 6 months, P =.16). A reduction of BE levels was present in patients with clinically inactive MS. Treatment with IFN-beta seems to induce an increase of this opioid in PBMCs of MS patients. The increase of BE concentration during a clinical relapse may represent a possible control mechanism aimed at counterbalancing the inflammatory phase of the disease. Arch Neurol. 2000;57:1178-1181

Cardiovascular and hormonal responses to hyperthermic stress in cocaine addicts after a long period of abstinence

In order to study the effects of exposure to heat, cardiovascular and hormonal responses were measured in 10 male cocaine addicts (after 4 weeks and 1 year of abstinence) and in 10 normal men. Subjects sat for 30 minutes in a sauna room. Hormonal (ACTH, beta endorphin, (beta EP) met enkephalin (met-enk), prolactin (PRL), cortisol) and cardiovascular parameters (heart rate, systolic and diastolic blood pressure) were measured before and after heat exposure. Basal levels of ACTH, beta EP, Met-Enk and cortisol were similar in normal and in cocaine addicts, whereas plasma PRL values were higher in drug abusers after long-term abstinence. All the examined hormones, with the exception of Met-Enk, were significantly raised in normal control subjects at the end of sauna. In contrast, no significant hormonal response to hyperthermia was observed in cocaine addicts either after 4 weeks and 1 year of abstinence. No changes were detected in heart rate and blood pressure in each group, indicating that the cardiovascular adaptive responses to hyperthermia in cocaine addicts was unaltered. The results of the present study provide evidence of an impairment of the hormonal response to hyperthermia in cocaine abusers. In conclusion, cocaine abuse produces alteration in the hypothalamic-pituitary function which persists after a long period of abstinence.