Search PubMed⌕ Search

Biomedical subjects

P Monteleone

Publications and source records attributed to P Monteleone.

At least 91 records · Page 5Linked to original sources

Failure of single electroconvulsive shock to affect daytime melatonin production in rats.

It has been reported that, in the rat, different types of stressful procedures increase daytime melatonin production. Electroconvulsive shock (ECS) has been shown not to affect daytime pineal melatonin in rats killed 9 hr after its administration. It is possible that the long-lasting interval between the ECS administration and the sacrifice of the animals obscured an effect of the stressful procedure. In the present study, the effects of acute ECS on daytime melatonin production were evaluated in both ECS- and sham-treated rats killed 30, 60, 120, and 240 min after treatment. As compared with the sham-treated animals, rats receiving acute ECS (80 mA, 0.5 sec) did not show any significant difference in either pineal or serum melatonin levels at any time point after treatment. These data indicate that single ECS does not affect daytime melatonin production in the rat and suggest that the pineal gland may respond differently to the various stressful procedures.

Analysis of Variance↗

Effects of trazodone on plasma cortisol in normal subjects. A study with drug plasma levels.

Trazodone is a novel antidepressant drug with alpha-adrenolytic activity. Since alpha 1-adrenoceptor mechanisms have been shown to stimulate basal cortisol secretion in healthy humans, the neuroendocrine effects of trazodone (75 mg orally) were evaluated in six healthy subjects. The drug plasma levels were also measured. With respect to placebo, trazodone significantly decreased plasma cortisol concentrations (F = 9.173, p less than 0.01). The areas under the curve (AUC) of plasma trazodone concentrations were negatively correlated with the AUC of plasma cortisol levels (r = -0.95, p less than 0.0005). These results confirm that, in humans, alpha 1-adrenergic mechanisms stimulate the basal secretion of cortisol.

Female↗

Chronic antidepressant drug treatment does not affect GH response to baclofen in depressed subjects.

The growth hormone (GH) response to baclofen, a specific GABAB agonist, was tested in 8 male depressed patients before and after chronic treatment with amitriptyline (100 mg/day). No difference was seen in plasma GH response before and 28 days after amitriptyline treatment, suggesting that chronic antidepressant drug treatment does not increase hypothalamic GABAB receptor sites in humans. These data suggest that further studies need to support the hypothesis of a GABA involvement in the mechanism of action of antidepressant drugs.

Adult↗

Evidence that cholinergic receptors of muscarinic type may modulate vasopressin release induced by metoclopramide.

Studies were carried out in the rat in order to investigate whether cholinergic mechanisms may be involved in vasopressin (VP) release induced by metoclopramide (MCP). The intravenous injection of MCP induced dose-related increases in plasma VP levels in water-loaded rats. These effects were prevented by atropine sulphate, but not by pirenzepine hydrochloride indicating that activation of cholinergic receptors of M-2 type was possibly required for the biologic response.

Animals↗

Physical exercise at night blunts the nocturnal increase of plasma melatonin levels in healthy humans.

The effects of physical exercise on nighttime melatonin secretion have never been investigated in humans. For this purpose, plasma melatonin levels were measured at different times during the day and the night in seven healthy men (aged 26-33 yrs), both in resting condition and before and after a physical exercise performed between 10.40 and 11.00 p.m.. The exercise consisted in bicycling on a bicycle ergometer at 50% of the personal maximal work capacity (MWC) for 10 min, followed by other 10 min of bicycling at 80% of the MWC. The results clearly showed that physical stress at night significantly blunts the nocturnal increase in plasma melatonin levels (group X time interaction: p less than 0.00001; two-way ANOVA with repeated measures). These findings, taken together with the data of the literature, suggest that the response of the pineal gland to provocative stimuli may depend on its level of activity when the stimulus is applied.

Adult↗

GABA, depression and the mechanism of action of antidepressant drugs: a neuroendocrine approach.

Recent evidence has suggested the involvement of the GABAergic system in depression and in the mechanism of action of somatic antidepressant treatments. In particular, GABAB receptors have been found to be increased in the rat frontal cortex following chronic antidepressant therapies. In the present study, the sensitivity of GABAB binding sites was assessed in nine healthy men and 10 depressed patients via the plasma growth hormone (GH) response to acute baclofen administration (20 mg p.o.). Depressed subjects were tested before and after 15 and 35 days of treatment with amitriptyline (100 mg/day), imipramine (100 mg/day) and fluoxetine (20 mg/day). GH response to acute GABAB receptor activation did not differ between depressed subjects and healthy controls. Moreover, chronic antidepressant treatment did not significantly modify this response, even when a clear therapeutic effect was obtained. These results do not support the idea that GABAergic mechanisms are involved in the pathophysiology of depression and in the mechanism of action of antidepressant drugs.

Adult↗

Plasma HVA, tardive dyskinesia and psychotic symptoms in long-term drug-free inpatients with schizophrenia.

Plasma homovanillic acid (pHVA) levels were measured in 16 chronically ill patients with schizophrenia who also suffered from tardive dyskinesia, and in a group of 14 chronically ill patients with schizophrenia who did not have tardive dyskinesia. All patients were studied following an extensive drug-free period (mean = 32.9 months). Patients with orofacial dyskinesia had significantly lower levels of pHVA than did controls. In patients without tardive dyskinesia, pHVA levels were significantly correlated with both positive and negative symptomatology. In contrast, pHVA levels from patients with tardive dyskinesia bore neither a significant nor a nearly significant relationship to symptomatology. The implications of these findings for dopaminergic models of tardive dyskinesia are discussed.

Aged↗

Evidence for a linear relationship between plasma trazodone levels and clinical response in depression in the elderly.

To investigate a possible relationship between plasma levels of trazodone and its clinical antidepressant effects, 11 elderly depressed patients underwent a 5-week treatment with 150 mg/day trazodone in three oral administrations. Clinical antidepressant response was assessed with two different clinical improvement criteria and plasma trazodone concentrations were determined by high-performance liquid chromatography. A significant correlation was found between steady-state plasma trazodone levels and its antidepressant efficacy, but not between plasma drug levels and the incidence of side effects. Moreover, the steady-state plasma trazodone concentration of 650 ng/ml was identified as threshold value for a greater occurrence of good antidepressant responses.

Administration, Oral↗

Dexamethasone suppression test in patients with primary obsessive-compulsive disorder and in healthy controls.

The dexamethasone suppression test (DST) was performed in 18 patients (11 women and 7 men) who met the DSM III-R criteria for obsessive-compulsive disorders (OCD), and in 20 healthy volunteers (12 women and 8 men). At 4.00 p.m., following dexamethasone administration, 5 patients (27.7%) and 1 healthy subject (5%) displayed plasma cortisol values well above the cut-off value of 50 ng/dl. A significantly different sex ratio was observed between suppressor and nonsuppressor patients with OCD (chi 2 = 4.40, p less than 0.03), because all nonsuppressor patients were male. Compared to the suppressors, nonsuppressor patients with OCD did not differ in any of the clinical and demographic variables investigated. Moreover, in our patient sample, the mean +/- SD total Hamilton Depression Rating Score (HDRS) was 14.8 +/- 2.5, and none of the nonsuppressors with OCD had a total HDRS greater than 17. These data suggest that a subgroup of OCD patients, particularly males, may escape the DST independently from the coexistence of depressive features.

Adolescent↗

Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans.

The activity of brain cortex-derived phosphatidylserine (BC-PS) on the neuroendocrine and neurovegetative responses to physical stress was tested in 8 healthy men who underwent three experiments with a bicycle ergometer. According to a double-blind design, before starting the exercise, each subject received intravenously, within 10 min, 50 or 75 mg of BC-PS or a volume-matched placebo diluted in 100 ml of saline. Blood samples were collected before and after the exercise for plasma epinephrine (E), norepinephrine (NE), dopamine (DA), adrenocorticotropin (ACTH), cortisol, growth hormone (GH), prolactin (PRL) and glucose determinations. Blood pressure and heart rate were also recorded. Physical stress induced a clear-cut increase in plasma E, NE, ACTH, cortisol, GH and PRL, whereas no significant change was observed in plasma DA and glucose. Pretreatment with both 50 and 75 mg BC-PS significantly blunted the ACTH and cortisol responses to physical stress.

Adrenocorticotropic Hormone↗

Lithium decreases retinal melatonin levels in the frog.

The effect of the acute i.p. administration of lithium chloride (1 mg/kg) and of haloperidol (1 mg/kg) on retinal melatonin levels was studied in light-adapted and dark-adapted frogs of the species Rana esculenta. Two hours following drug administration, animals were killed by decapitation and a single retina from each frog was collected and homogenized in 1 ml of chilled 0.1 N HCl. After centrifugation, the pH of the supernatant was adjusted to 7.0. Melatonin was extracted by diethylether and assayed by double antibody radioimmunoassay (RIA). Lithium induced a significant decrease of retinal melatonin levels both in light-adapted (P less than 0.006) and in dark-adapted (P less than 0.01) animals, whereas no change was observed after haloperidol treatment. These results suggest that the scleral aggregation of pigment granules induced by lithium in the frog retina is not mediated by a stimulation of melatonin synthesis.

Animals↗

Preliminary observations on the suppression of nocturnal plasma melatonin levels by short-term administration of diazepam in humans.

Several studies suggest that GABAergic mechanisms may be involved in the modulation of melatonin secretion. However, conflicting results have been reported in animal studies; in humans the issue has not been widely investigated. In the present study, using a double-blind design, six healthy men received orally, at midnight, 10 mg of diazepam, a GABAergic agent, or placebo, on two different occasions 1 week apart. Blood samples were collected, in the dark, immediately before the drug administration, and at 12:30, 1, 2, 3, and 4 AM. Serum melatonin was measured by a radioimmunological method with [125I]melatonin as a tracer. Two-way ANOVA with repeated measurements disclosed a significant effect for treatment (P less than 0.01), for time (P less than 0.0004), and for treatment X time interaction (P less than 0.05). Following diazepam administration, serum melatonin levels observed at 2, 3, and 4 AM were significantly lower than the corresponding values following placebo (P less than 0.002 at 2 and 4 AM; P less than 0.03 at 3 AM [Students' paired t test]). These results show that nocturnal blood melatonin levels may be suppressed by the acute administration of a GABAergic agent, suggesting that GABA may be involved in the modulation of pineal activity in man.

Adult↗

Repetitive growth hormone-releasing hormone administration restores the attenuated growth hormone (GH) response to GH-releasing hormone testing in normal aging.

The plasma GH response to human pituitary GH (hpGH)-releasing hormone-40 (hpGHRH-40; 1 microgram/kg BW) was significantly lower in seven healthy aged men (age range, 65-78 yr) than in seven healthy young men (age range, 18-31 yr) 30, 60, and 90 min after acute hpGHRH-40 administration (P less than 0.0001, by Student's unpaired t test). To verify whether a priming regimen might be able to reverse the reduced GH response to GHRH, elderly subjects underwent repetitive administration of hpGHRH-40 and placebo in a double blind design (100 micrograms hpGHRH-40 or volume-matched saline iv as a single morning dose, every 2 days for 12 days). After the hpGHRH-40-priming regimen, plasma GH values 30, 60, and 90 min after the acute GHRH test were significantly higher than values at the corresponding time points after placebo treatment. These findings suggest that somatotroph cells become less sensitive to GHRH with normal aging and demonstrate that repetitive administration of GHRH restores the attenuated response.

Adult↗

Plasma trazodone concentrations and clinical response in elderly depressed patients: a preliminary study.

Steady-state plasma levels of trazodone were determined by HPLC in 11 elderly depressed patients who underwent a 5-week pharmacological treatment with 150 mg/day trazodone in three oral administrations. Clinical antidepressant response, assessed with three different clinical improvement criteria, was significantly correlated with steady-state plasma trazodone concentrations. Moreover, the steady-state plasma trazodone concentration of 650 ng/ml was identified as the threshold value for a good antidepressant response. No correlation was found between the occurrence of side effects and plasma levels of trazodone.

Administration, Oral↗

Neuroanatomical and biochemical evidence for the involvement of the area postrema in the regulation of vasopressin release in rats.

Studies were carried out in the rat to determine if the area postrema (AP), a medullary circumventricular organ, might be involved in the control of vasopressin (VP) release. The data from this study demonstrate the existence of direct neural connections between the AP and the hypothalamic VPergic neurons of the supraoptic nucleus (SON) as showed by the retrograde tracer horseradish peroxidase (HRP). Labeled neurons were observed in the AP following HRP injections into the SON. In addition, rats with AP lesions showed an impaired ability to conserve water and concentrate their urine in response to an hypertonic NaCl load. They, also, failed to maintain sodium retention and showed an attenuation of VP release during intracellular dehydration. These findings indicate that AP plays an important role in the regulation of VP release during changes in osmotic environment and suggest that this medullary circumventricular organ is a part of central circuitry subserving salt-water balance.

Animals↗

Prolactin response to sodium valproate in schizophrenics with and without tardive dyskinesia.

Sodium valproate, a GABAergic agent (800 mg), and placebo were administered orally, as a single dose, to nine chronic schizophrenics with tardive dyskinesia (TD), seven chronic schizophrenics without TD and ten healthy controls, according to a double blind design. Blood samples were collected before and after drug administration, to determine plasma prolactin concentrations. Sodium valproate decreased plasma prolactin levels in healthy subjects (P less than 0.001) and in schizophrenic patients with TD (P less than 0.001), but not in chronic schizophrenics without TD. Moreover, in dyskinetic subjects, the maximum per cent decrease of plasma prolactin from basal value was positively correlated to the score of the abnormal involuntary movement scale (r = 0.724, P less than 0.02). Although the neural or biochemical substrate underlying the different responses of plasma prolactin to sodium valproate in schizophrenics with and without TD remains unclear, these results provide the first neuroendocrine evidence able to differentiate dyskinetic subjects from those without TD within a schizophrenic population.

Adult↗

Baclofen-induced growth hormone secretion is blunted in chronic schizophrenics: neuroendocrine evidence for a GABA disturbance in schizophrenia.

To substantiate a previously reported disturbance of gamma-aminobutyric acid (GABA) in chronic schizophrenia, plasma growth hormone (GH) response to a direct GABA agonist (baclofen, 10 mg) was assessed in 12 unmedicated chronic schizophrenic males and 10 sex- and age-matched healthy controls. Baclofen and placebo were administered orally, in a double-blind design, and blood samples were collected before and 30, 60, 90, 120, 180, and 240 min after drug or placebo administration. Baclofen induced a clear-cut rise in plasma GH levels over baseline values, but the GH increase observed in the patients was significantly smaller than that in controls. These results support the idea that GABA mechanisms may be impaired in chronic schizophrenia.

Adult↗

Lateralization patterns of verbal stimuli processing assessed by reaction time and event-related potentials in schizophrenic patients.

Event-related potentials (ERPs), reaction time (RT), number of errors and number of omissions were recorded by using a visual target detection paradigm in which consonant pairs were presented in a central and in a lateral condition. Fourteen DSM III drug-free schizophrenics and 19 healthy subjects took part in the study. All of them were male and right-handed. Independent principal component analysis and varimax rotation were performed for each condition. Separate ANOVAs were performed on factor scores computed for each rotated principal component. In the central condition, schizophrenic patients showed a reduction of the late positive complex (LPC) peak with respect to normal controls, and this reduction was associated with a predominant negative symptomatology. No pattern of lateral asymmetry was found in either group for behavioural and ERP measures. For the lateral condition, a significant advantage of the right visual field (RVF) presentation (shorter RT and larger LPC peak for RVF stimuli) was observed in normal subjects, while no visual field effect on these two measures was detected in schizophrenics. Significant differences were found between the two groups on both behavioural and ERP measures for the RVF only. Furthermore, two ERP components showed a marked advantage of the left visual field in the patient group, associated with a predominance of positive symptoms in the clinical picture.

Adult↗