Lack of effect of short-term fluoxetine administration on nighttime plasma melatonin levels in healthy subjects.
Explore the source record for details and available documents.
Administration, Oral↗
Biomedical subjects
P Monteleone
Publications and source records attributed to P Monteleone.
Seasonal variations in the daily rhythm of melatonin and NAT activity in the Harderian gland, retina, pineal gland, and serum of the green frog, Rana esculenta.
Day-night variations of melatonin content and N-acetyltransferase (NAT) activity were studied in the Harderian gland (HG), retina, pineal gland, and serum of the green frog Rana esculenta. Throughout the year the retinal melatonin content was correlated with retinal NAT activity and was always higher than those in the pineal gland and HG. On the other hand, in these structures diurnal fluctuations in NAT activity were observed. There were clear seasonal differences in the magnitude of the nocturnal increase of retinal melatonin levels as well as in the nocturnal pattern of retinal NAT activity. In summer day-night variations of melatonin and NAT are absent. The prevailing photoperiod seems to affect melatonin and NAT circadian rhythms in R. esculenta.
Animals↗
Role of seizure activity in the decreased pineal response to isoproterenol in rats chronically treated with electroconvulsive shock.
Chronic electroconvulsive shock (ECS) has been previously reported to blunt the melatonin response to acute isoproterenol administration in rats. To assess whether electrically induced seizures are indeed required for the appearance of the blunted pineal response to isoproterenol, pineal and serum melatonin levels were measured after isoproterenol stimulation in rats treated with ECS (80 mA, 0.5 sec), subconvulsive shock (15 mA, 0.5 sec), or sham-ECS once per day at 11:30-12:00 h for 8 days. In ECS-treated rats, both pineal and serum melatonin levels after isoproterenol administration were significantly lower than those in sham-treated animals and in rats receiving subconvulsive shock. Moreover, as compared with sham treatment, chronic subconvulsive shock did not affect the melatonin response to isoproterenol. These data show that seizure activity is indeed required for the ECS-induced decrease in the pineal response to acute beta-adrenergic stimulation.
Animals↗
Blood levels of mianserin and amitriptyline and clinical response in aged depressed patients.
Steady-state plasma levels of mianserin, amitriptyline, and nortriptyline were determined by HPLC in two groups of elderly depressed patients who underwent a 5-week treatment with mianserin (60 mg/day in three oral doses) or amitriptyline (75 mg/day in three oral doses). Both treatments proved to be effective in reducing depressive symptoms. In the mianserin group, responder patients had steady-state plasma concentrations of mianserin higher than nonresponders. No relationship was found between amitriptyline, nortriptyline, or amitriptyline+nortriptyline plasma levels and clinical response in amitriptyline treated patients.
Aged↗
Circadian rhythms of melatonin, cortisol and prolactin in patients with obsessive-compulsive disorder.
Plasma melatonin, cortisol and prolactin (PRL) levels were measured over a 24-h period in 13 drug-free patients with obsessive-compulsive disorder and in matched healthy subjects. The circadian profiles of melatonin and PRL were altered in patients; the circadian rhythm of cortisol was preserved, although at a higher level compared with normal controls. These changes were significantly related to the severity of the obsessive-compulsive symptoms. Further studies need to clarify the state- or trait-dependent character of these abnormalities.
Adult↗
Seasonal variation in the dexamethasone suppression test: a longitudinal study in chronic schizophrenics and in healthy subjects.
To evaluate seasonal influences on the dexamethasone suppression test (DST), cortisol and melatonin responses to dexamethasone were assessed in drug-treated chronic schizophrenics and in drug-free healthy volunteers in different seasons of the year, according to a longitudinal study design. In schizophrenic patients, there was a greater rate of cortisol non-suppression to DST in February as compared to November and May (chi 2 = 4.5, p = 0.03) with no significant differences in pre- and post-dexamethasone plasma cortisol levels. In healthy volunteers, in contrast, no seasonal variation in DST results was observed. Moreover, dexamethasone administration did not significantly affect morning plasma melatonin levels in either patients or healthy controls. These findings suggest that seasonality may be of critical importance in evaluating DST results in schizophrenic patients, but not in healthy subjects.
Adult↗
[Evaluation of therapeutic efficacy and pharmacokinetics of controlled release of trazodone in patients with major depressive disorder].
In the present study, the antidepressant efficacy of a controlled-release (CR) formulation of trazodone was evaluated in 18 depressed patients treated with 150 mg (no. = 10) or 75 mg (no. = 8) nocte doses of the drug for 7 weeks, according to an open design. Drug plasma levels were evaluated on days 7, 14, 28 and 35 of treatment. Moreover, at the end of treatment, the plasma concentration-time curve of the CR trazodone was assessed. CR trazodone was effective in improving depressive and anxious symptomatology as well as in ameliorating the quality of sleep in 13 patients with a low incidence of side effects. Nonresponder subjects had morning plasma levels of trazodone below the value of 650 ng/ml. The pharmacokinetic profile of CR trazodone, observed after 35 days of treatment, may account for both the low occurrence of untoward side effects and the therapeutic efficacy of the single dose at nighttime.
Adult↗
The human pineal gland responds to stress-induced sympathetic activation in the second half of the dark phase: preliminary evidence.
Previous reports by our group and by others showed that the human pineal gland is unresponsive to stress-induced systemic sympathetic activation either during the day or 3 hrs after the beginning of darkness. In the present study, we investigated whether a longer period of dark exposure is required to demonstrate a stimulatory effect of stress-induced sympathetic activation on the human pineal gland. For this purpose, plasma melatonin levels were measured in six healthy men (aged 25-34 yrs) both in resting condition and before and after a physical exercise performed between 02.40 and 03.00 h, 30 min after exposure to bright light (2000 lux). Light exposure lasted from 02.10 h up to 04.00 h. The exercise consisted in bicycling on a bicycle ergometer at 50% of the personal maximum work capacity (MWC) for 10 min, followed by another 10 min of bicycling at 80% of the MWC. In the same subjects, plasma melatonin levels were measured also without exposure to light and with no exercise (control dark condition). The results showed that physical exercise, although inducing a rapid and short-term general sympathetic activation (as shown by significant changes in cardiovascular parameters) was able to increase light-depressed plasma melatonin levels only 5 hrs after the end of the stress (p < 0.0001, group X time interaction, two-way ANOVA with repeated measures). These findings suggest that the human pineal gland is responsive to systemic sympathetic activation induced by physical stress in the second half of the dark phase.
Adult↗
Pharmacokinetic and pharmacodynamic characteristics of a controlled-release formulation of trazodone versus the conventional formulation in healthy volunteers.
The pharmacokinetic and pharmacodynamic characteristics of a controlled-release (CR) formulation of trazodone were evaluated in healthy subjects who received acutely 150 mg and 75 mg of the CR trazodone and equal amounts of the conventional formulation on separate occasions. Plasma trazodone concentrations were measured by HPLC. The pharmacokinetic profile of CR trazodone was characterized by a slower increase in drug plasma levels and a lower and retarded peak plasma concentration without any modification in the total amount of trazodone absorbed over 24 hrs. The side effects were less severe and less frequent than with the conventional formulation.
Adult↗
Pineal response to isoproterenol in rats chronically treated with electroconvulsive shock.
Chronic electroconvulsive shock (ECS) has been shown to induce a downregulation of beta 1-adrenergic receptors in the rat cerebral cortex. Because the secretion of melatonin in the pineal gland is regulated primarily by beta 1-adrenoceptors, in the present study we investigated the effect of chronic administration of ECS on pineal beta-adrenergic responsiveness to isoproterenol. To this purpose, young adult male rats received once daily for 8 days ECS (80 mA, 0.5 s) or sham ECS. On the day after the last ECS or sham treatment, they were injected with isoproterenol hydrochloride (1 mg/kg SC) or volume-matched saline at 1600 h. Two hours later they were killed by decapitation. Results showed that the isoproterenol-induced increase in the pineal melatonin content was blunted in rats treated with ECS as compared to sham-treated animals (shock x drug interaction = p < 0.01). These data indicate that chronic ECS treatment affects beta 1 receptor-mediated melatonin production in the pineal gland. Further studies need to elucidate whether the blunted melatonin response to isoproterenol in ECS-treated rats is due to a downregulation of pinealocyte beta-adrenergic receptors.
Analysis of Variance↗
A comparative study of melatonin production in the retina, pineal gland and harderian gland of Bufo viridis and Rana esculenta.
1. The circadian patterns of melatonin and of its synthesizing enzyme N-acetyltransferase (NAT) were investigated in the serum, retina, pineal gland and Harderian gland (HG) of two amphibian species, Bufo viridis and Rana esculenta. 2. Serum melatonin levels showed no diurnal fluctuations in Bufo viridis, whereas, in Rana esculenta, they exhibited a circadian rhythm, with the highest values occurring during the night. Retina melatonin exhibited characteristic circadian patterns in both species, with the highest values occurring during the day, in Bufo, and the highest concentrations occurring at night in Rana. 3. In the retina, NAT activity peaked at night in both amphibians, but in Bufo the levels were up to 30 times higher than in Rana. In the HG and in the pineal gland, NAT activity showed different patterns in the two species with no diurnal variations in Bufo, and characteristic circadian rhythms in Rana. 4. In the HG and pineal gland of both species, melatonin was only occasionally detectable over the 24-hr period. 5. This is the first report exploring melatonin production in Bufo viridis and Rana esculenta. In our experimental conditions, marked differences emerged between the two species.
Animals↗
Blunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy men.
The effect of chronic administration of phosphatidylserine derived from brain cortex on the neuroendocrine responses to physical stress has been examined in a placebo-controlled study in 9 healthy men. Phosphatidylserine 800 mg/d for 10 days significantly blunted the ACTH and cortisol responses to physical exercise (P = 0.003 and P = 0.03, respectively), without affecting the rise in plasma GH and PRL. Physical exercise significantly increased the plasma lactate concentration both after placebo and phosphatidylserine. The results suggest that chronic oral administration of phosphatidylserine may counteract stress-induced activation of the hypothalamo-pituitary-adrenal axis in man.
Administration, Oral↗
Melatonin and cortisol secretion in patients with primary obsessive-compulsive disorder.
Plasma levels of melatonin and cortisol were measured over a 24-hour period in seven patients with primary obsessive-compulsive disorder (OCD) and seven matched healthy control subjects. In OCD patients, the 24-hour secretion of melatonin was reduced as compared with that in healthy control subjects, whereas its circadian rhythm was preserved. In addition, in OCD patients, the overall secretion of cortisol was higher than that in control subjects, but there was no change in the circadian pattern of cortisol secretion. No correlation was found between clinical parameters and hormone levels.
Adult↗
Temporal relationship between melatonin and cortisol responses to nighttime physical stress in humans.
It has been shown that, in the rat, physical stress decreases pineal melatonin levels at night, whereas it increases melatonin production during the day. We have demonstrated that nighttime physical exercise is able to blunt the nocturnal surge of plasma melatonin in healthy subjects. Since this effect might be mediated by exercise-induced cortisol secretion from the adrenal gland, in the present investigation we studied the relationship between cortisol and melatonin responses to nighttime physical stress in six healthy men, aged 28-33 yr. The physical stress consisted of bicycling on a bicycle ergometer at 50% of personal maximum work capacity (MWC), followed by another 10 min of bicycling at 80% of MWC. According to our previous data, physical exercise performed between 2240 h and 2300 h significantly reduced the nocturnal surge of plasma melatonin and increased the levels of cortisol. The surge in plasma cortisol preceded the decrease in plasma melatonin concentration. These findings suggest a temporal relationship between plasma cortisol and melatonin responses to physical stress; the causal nature of this relationship remains to be elucidated.
Adult↗
Depressed nocturnal plasma melatonin levels in drug-free paranoid schizophrenics.
The 24-h profiles of plasma melatonin and cortisol were evaluated in 7 drug-free male paranoid schizophrenics and in 7 healthy subjects matched to the patients for age, sex, body weight, height and season of testing. Blood samples were obtained at 20.00, 22.00, 24.00, 01.00, 02.00, 06.00, 08.00 and 12.00 h. Light was turned off from 21.00 to 07.00 h. Compared with that of the normal controls, the circadian rhythm of plasma melatonin was absent in paranoid schizophrenics (F7.84 = 7.30, p less than 0.0001; two-way ANOVA with repeated measures) whereas the 24-h profile of plasma cortisol was preserved, although at a slightly higher level (F1.12 = 26.810, p less than 0.0002). The melatonin/cortisol ratio was significantly higher in healthy subjects than in the schizophrenic patients. A functional relationship between disturbances in the melatonin rhythm especially and schizophrenia may be proposed, although the significance of this relationship remains to be elucidated.
Adult↗
Physical stress in the middle of the dark phase does not affect light-depressed plasma melatonin levels in humans.
The human pineal gland has been shown to be unresponsive to stress-induced sympathetic activation during the day. However, the effects of stress on human melatonin production have received little investigation at night, when the pinealocytes should be physiologically responsive to noradrenergic stimulation. For this purpose, plasma melatonin and cortisol levels were measured in 7 healthy men (aged 25-34 years), both in resting condition and before and after a physical exercise performed between 23.40 and 24.00 h, 30 min after exposure to bright light (2,500 lx). The exercise consisted in bicycling on a bicycle ergometer at 50% of the personal maximum work capacity (MWC) for 10 min, followed by another 10 min of bicycling at 80% of the MWC. The results clearly showed that physical exercise does not affect light-depressed plasma melatonin levels, whereas it clearly increased plasma cortisol concentrations (p less than 0.002, two-way ANOVA with repeated measures), systolic blood pressure, pulse pressure and heart rate. These findings suggest that the human pineal gland is not responsive to systemic sympathetic activation induced by physical stress even in the middle of the dark phase.
Adult↗
Reduced lymphocyte response to PHA and OKT3 in drug-free and neuroleptic-treated chronic schizophrenics.
Explore the source record for details and available documents.
Adult↗
Impaired sensitivity of the hypothalamo-pituitary-thyroid axis to the suppressant effect of dexamethasone in elderly subjects.
It has been shown that glucocorticoids have a suppressant effect on the thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) in young men. To assess whether this effect of corticosteroids is also present in aged individuals, six young subjects (aged 26-32 years) and six elderly men (aged 68-75 years) underwent, in random order, at 1 week intervals, three TRH stimulation tests 30 min after IV administration of placebo and 2 mg and 4 mg dexamethasone phosphate. Elderly men showed higher basal plasma levels of TSH (P less than 0.02) and lower plasma levels of FT3 (P less than 0.03) and FT4 (P less than 0.01). The TSH response to TRH was significantly lower in aged subjects than in young ones (P less than 0.009). Moreover, 2 mg dexamethasone significantly blunted the TSH response to TRH in young men (P less than 0.0001), but not in the elders. The inhibitory effect of the glucocorticoid on the TRH-induced TSH secretion, in aged subjects, was evident only after 4 mg dexamethasone administration (P less than 0.0001). These data confirm that glucocorticoids have an inhibitory role on the thyrotropic axis and show, for the first time, that normal elderly men are hyporesponsive to this suppressant effect of corticosteroids.
Adult↗