Naloxone decreases the inhibitory effect of alprazolam on the release of adrenocorticotropin/cortisol induced by physical exercise in man.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: • Alprazolam (ALP), a benzodiazepine activating GABAergic receptors, is involved in ACTH secretion. WHAT THIS STUDY ADDS: • This study demonstrates a partial opioid influence in the inhibitory effect of ALP on the release of ACTH/cortisol during physical exercise. AIMS: To establish the possible involvement of alprazolam (ALP) and/or opiates in the mechanism underlying the ACTH/cortisol response to physical exercise. METHODS: Tests were carried out under basal conditions (exercise control test), exercise plus ALP (50 µg at time -90 min), naloxone (10 mg at time 0) or ALP plus naloxone. Plasma ACTH and serum cortisol concentrations were evaluated in blood samples taken before, during and after the bicycle ergometer tests. RESULTS: ACTH and cortisol concentrations rose significantly after physical exercise. Maximum peak at time 15 min (P ≤ 0.01 vs. baseline) for ACTH and at time 30 min (P ≤ 0.01 vs. baseline) for cortisol. In the presence of naloxone, the ACTH and cortisol responses were significantly increased (maximum peak at time 20 min, P ≤ 0.02 vs. control test for ACTH, and at time 30 min (P ≤ 0.01 vs. baseline) for cortisol) whereas they were abolished by ALP. When ALP and naloxone were given together, the inhibitory effect of ALP was partial. CONCLUSIONS: These data demonstrate an inhibitory effect of ALP in the regulation of the ACTH/cortisol response to physical exercise in man and suggest that GABAergic receptor activating benzodiazepines and opioids interact in the neuroendocrine secretion of ACTH/cortisol.

Inhibitory effect of dexamethasone on arginine-vasopressin release induced by physical exercise in man.

To establish whether glucocorticoids inhibit the arginine-vasopressin (AVP) response to physical exercise, 10 healthy men underwent bicycle ergometer tests until exhaustion (exercise control test, exercise plus dexamethasone [2 or 4 mg in an intravenous bolus]). Physiological and biochemical variables were similar in all tests. Pretreatment with dexamethasone (2 or 4 mg) partially but significantly decreased the AVP response induced by physical exercise. Our results demonstrate a partial inhibition induced by glucocorticoids of AVP neurosecretion during cycle ergometer tests.

Effect of naloxone on the inhibitory effect of melatonin on the release of arginine-vasopressin induced by physical exercise in man.

This study was performed in order to establish whether endogenous opioids play a role in the inhibitory effect of melatonin on arginine-vasopressin (AVP) response to physical exercise. Seven healthy men underwent four bicycle ergometer tests until exhaustion [exercise control test, exercise plus naloxone (2mg injected plus 5mg infused intravenously), exercise plus melatonin (6mg), exercise plus melatonin plus naloxone]. Plasma AVP concentrations, non endocrine physiological parameters (NEPP) and biochemical parameters were evaluated during all tests. NEPP and biochemical values had a similar pattern during all tests. Physical exercise significantly increased the AVP levels. The pre-treatment with melatonin inhibited the AVP response to physical exercise. In contrast, naloxone had no effect on AVP rise during exercise, when given alone, whereas it abolished the negative effect of melatonin on AVP response to physical exercise. Our data indicate that naloxone-sensitive endogenous opiates mediate the inhibitory modulation exerted by melatonin on the AVP response to physical exercise.

Effect of physical training on age-related reduction of GH secretion during exercise in normally cycling women.

OBJECTIVE: To evaluate whether prolonged physical activity (25 km/week running for 8 years) modifies GH decline. DESIGN: The GH response to maximal exercise on bicycle-ergometer was tested in younger (26-30 years) and older (42-46 years) healthy women. Each age group included 2 subgroups of 10 sedentary and 10 runners, which were compared. The workload was increased at 3 min intervals from time 0 until exhaustion. Subjects with a low maximal capacity (as established in a preliminary test) pedalled for 3-4 min against no workload at the beginning of the test, so that exercises lasted about 15 min in all individuals. RESULTS: At exhaustion, heart rate and systolic pressure were significantly higher in sedentary than in trained subjects, whereas V(O(2)max), blood glucose and plasma lactate levels were similar in all groups. Exercise induced similar GH responses in younger sedentary and exercise-trained subjects and in older exercise-trained subjects, with mean peak levels 7.5 times higher than baseline. In contrast, in older sedentary women peak GH level was only 4.4 times higher than baseline and was significantly lower than in the other groups. CONCLUSION: These data suggest that in women prolonged physical training exerts protective effects against age-dependent decline in GH secretion.

Effects of moderate ethanol drinking on the GH and cortisol responses to physical exercise.

OBJECTIVE: To evaluate the effects of moderate amounts of ethanol on the GH and cortisol responses to physical exercise. METHODS: Ten normal men underwent three bicycle ergometer tests. Test were carried out in basal conditions (control test) or after drinking 0.5 or 0.75 g/kg BW ethanol. Tests lasted 15 min in all subjects; the workload was increased at 3 min intervals from time 0 until exhaustion. Non-endocrine physiological parameters (NEPP), such as heart rate, blood pressure, ventilation, frequency of breathing, tidal volume, oxygen consumption, carbon oxide production and respiratory exchange ratio were measured from time 0 until exhaustion. Serum GH and cortisol levels were evaluated in blood samples taken at 5-10 min intervals over a 50 min period from time 0. RESULTS: Neither basal values, nor exercise-induced changes in NEPP were altered by ethanol drinking. Both GH and cortisol levels significantly rose during the exercise control test. The hormonal responses did not change after 0.5 g/kg BW ethanol, whereas they significantly decreased after 0.75 g/kg BW ethanol. CONCLUSIONS: Modification of the GH and cortisol responses to exercise represents an "endocrine window" of the effects that even moderate ethanol drinking produces in the CNS. The data show that 0.75 g/kg BW ethanol is the minimal amount producing significant inhibitory effects on the GH and cortisol responses to physical exercise. In view of the important roles played by GH and cortisol during physical activity, even moderate ethanol drinking must be avoided before sport.

Adrenocorticotropic hormone/cortisol response to physical exercise in abstinent alcoholic patients.

BACKGROUND: Alterations in the hypothalamic-pituitary-adrenal (HPA) axis in alcoholic patients have been reported in various experimental conditions. METHODS: To establish whether alcoholism affects the HPA axis activation during physical exercise, 10 recent abstinent alcoholic patients (age range: 33-45 years; duration of alcohol dependence: range 4-6 years) were tested by exercising on a bicycle ergometer. Ten age-matched healthy nonalcoholic men participated as controls. The workload was gradually increased at 3-minute intervals until exhaustion and lasted about 15 minutes for all subjects. Alcoholic patients were tested at 3 time points, at 4, 6, and 8 weeks after alcohol withdrawal, whereas controls were tested only once. Main outcome measurements were circulating levels of adrenocorticotropic hormone (ACTH) and cortisol and physiological variables during physical exercise [heart rate, blood pressure, ventilation, frequency of breathing, tidal volume, oxygen consumption (VO2), carbon oxide production (VCO2), and respiratory exchange ratio (R)]. RESULTS: Similar basal and exercise-induced changes in physiological variables were observed in controls and alcoholic patients in all tests. Basal levels of ACTH and cortisol were similar in all tests performed on alcoholic patients and on normal controls. In normal subjects, exercise induced a significant increase in plasma ACTH and serum cortisol levels, with peak levels at 20 minutes for ACTH (84% higher than baseline) and at 30 minutes for cortisol (70% higher than baseline). After 4 weeks of abstinence, slight but not significant ACTH/cortisol responses to physical exercise were observed in alcoholic patients (mean peaks were 10 and 18% higher than baseline, respectively, for ACTH and cortisol). By contrast, when the exercise test was repeated after 6 weeks abstinence, ACTH/cortisol levels rose significantly versus baseline (mean peak levels of ACTH and cortisol were 48 and 38% higher than baseline, respectively, for ACTH and cortisol). However, the hormonal responses were significantly lower than in the normal controls. At 8 weeks of abstinence, ACTH/cortisol responses were significantly higher than 2 weeks previously, and were not distinguishable from the increments observed in the normal controls (76 and 68% higher than baseline, respectively, for ACTH and cortisol). CONCLUSIONS: In concurrence with previous reports showing alterations of the HPA axis in the central nervous system in alcohol-dependent subjects, these data show a defect of the neuroendocrine mechanism(s) underlying the ACTH/cortisol response to physical exercise for at least a month after alcohol withdrawal, with reconstitution of a normal hormonal response at 8 weeks.