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Biomedical subjects

G Bagdy

Publications and source records attributed to G Bagdy.

At least 55 records · Page 3Linked to original sources
PubMed1989

Delayed effects of chronic cortisol treatment on brain and plasma concentrations of corticotropin (ACTH) and beta-endorphin.

The effects of 2-day and 7-day cortisol treatment on immunoreactive corticotropin (ACTH) and beta-endorphin concentrations were measured in the cerebral cortex, hippocampus, hypothalamus, and cerebellum in male rats. Plasma ACTH, beta-endorphin, corticosterone, and cortisol levels were also measured in parallel. Cortisol administration by osmotic minipumps (25 mg/kg/day) maintained a constant, moderately high concentration (23.0 +/- 2.7 micrograms/100 ml) of this glucocorticoid in plasma. Two-day cortisol treatment suppressed the plasma concentration of ACTH and corticosterone, and also decreased, to a lesser degree, concentrations of beta-endorphin. ACTH and beta-endorphin levels in the brain remained unchanged after 2 days of cortisol treatment. After 7-day treatment, however, plasma concentrations of ACTH and beta-endorphin further decreased, while ACTH and beta-endorphin concentrations in the cortex and beta-endorphin concentrations in the cerebellum were also significantly decreased. Peptide concentrations in other brain areas did not change significantly with either 2-day or 7-day cortisol treatment. These data suggest that there are delayed effects of glucocorticoids on pro-opiomelanocortin peptide secretion and/or metabolism in the central nervous system. These findings are consistent with the impaired cognitive functions of patients with diseases, such as Cushing's syndrome and depression, that have long-lasting elevated cortisol secretion.

Adrenocorticotropic Hormone↗
PubMed1989

Prolactin response to fentanyl in depression.

Ten unmedicated female inpatients with major depression (DSM-III) and 10 healthy volunteer women were given an intravenous injection of 0.1 mg fentanyl at 9:00 AM and 9:00 PM on different days. The prolactin secretory response to this opioid agonist was investigated for 1 h with serial blood sampling. Repeated measures Analysis of Variance yielded a significant effect of fentanyl administration on prolactin secretion (p less than 0.0001), and there were elevated hormone responses in the evening (p less than 0.005). No group difference was seen between healthy volunteers and depressed patients, but four of the depressives showed the most blunted response, and three of these low responders committed suicide within 1 year.

Adult↗
PubMed1989

Opposite effects of chronic cortisol treatment on pre- and postsynaptic actions of clonidine in pithed rats.

1. Both clinical and experimental studies have shown that chronic elevation of plasma cortisol levels are attended by altered adrenergic receptor function. In the present study we examined the effects of chronic cortisol treatment (25 mg kg-1 day-1 for 7 days by minipumps) on the peripheral cardiovascular responses of pithed, adrenal demedullated vagotomized rats. 2. Chronic cortisol treated rats had higher basal diastolic blood pressures after being pithed, suggesting that sympathetic outflow is not required to sustain elevated peripheral resistance in glucocorticoid-induced hypertension. 3. Whereas alpha 1-adrenoreceptor-mediated diastolic blood pressure responses were unaltered, alpha 2-adrenoreceptor-mediated vasopressor responses were potentiated in pithed rats which were chronically treated with cortisol. 4. Elevation of plasma noradrenaline induced by the stimulation of the entire sympathetic outflow of pithed rats was not changed but the clonidine-induced presynaptic alpha 2-adrenoreceptor inhibition of noradrenaline release was attenuated by chronic cortisol treatment. 5. In conclusion, in adrenal demedullated pithed rats the responses mediated by peripheral pre- and postjunctional alpha 2-adrenoreceptors appeared to be affected oppositely after chronic cortisol treatment, suggesting that the pharmacologically homogeneous alpha 2-adrenoreceptor population may be modulated differently by chronic elevation of plasma glucocorticoids.

Adrenergic alpha-Agonists↗
PubMed1989

Marked increases in plasma catecholamine concentrations precede hypotension and bradycardia caused by 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in conscious rats.

Plasma noradrenaline and adrenaline responses to 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), a selective putative 5-HT1A receptor agonist, have been studied in conscious, freely moving rats. Intravenously administered 8-OH-DPAT caused dose-related and sustained increases in plasma noradrenaline (2-fold) and adrenaline (11-fold) concentrations. Neither metergoline pretreatment (0.5 mg kg-1 i.v.) nor splanchnicectomy had any effect on the noradrenaline and adrenaline elevation caused by 8-OH-DPAT (250 micrograms kg-1 i.v.). The catecholamine responses peaked early but were still present during nadirs in blood pressure and heart rate. The discrepancy between plasma catecholamine and cardiovascular changes raises further questions about the mechanism of action of 8-OH-DPAT and supports other evidence suggesting a role for vagus stimulation in the cardiovascular effects caused by this drug.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Long-term cortisol treatment impairs behavioral and neuroendocrine responses to 5-HT1 agonists in the rat.

The effects of chronic cortisol treatment on neuroendocrine and behavioral responses to serotonin1 (5-HT1) receptor agonists were studied in conscious, freely moving rats. Seven-day cortisol treatment (25 mg/kg/day with osmotic minipumps) markedly suppressed basal plasma corticotropin (ACTH) and corticosterone concentrations, indicating a suppression of the hypothalamo-pituitary-adrenocortical axis. Cortisol also decreased body weight, food intake, plasma norepinephrine (NE), and epinephrine (E) levels. In the drug challenge studies, we used two 5-HT1 agonists, the 5-HT1B and 5-HT1C agonist, m-chlorophenylpiperazine (m-CPP), and the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT), to examine the effect of cortisol on their behavioral and neuroendocrine effects. After 7-day cortisol treatment, plasma prolactin responses to both m-CPP and 8-OHDPAT were significantly decreased. While the plasma NE, E, and food intake responses to m-CPP were also significantly reduced by cortisol treatment, these same responses to 8-OHDPAT were unchanged. The effect of m-CPP on locomotor activity was also decreased. Since only the responses to m-CPP and 8-OHDPAT previously shown to be antagonized by pretreatment with the 5-HT1/5-HT2 antagonist, metergoline, were significantly attenuated after cortisol treatment, these changes may be specific to 5-HT receptors. These data indicate that chronic exposure to high glucocorticoid levels alters 5-HT1 receptor-mediated functions and provides additional evidence relevant to the contribution of glucocorticoid elevation to the symptoms of depression.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Multivariate analysis of monoamine indices in patients with chronic schizophrenia.

Levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), noradrenaline (NA), 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid and serum levels of prolactin (PRL) and dopamine-beta-hydroxylase (DBH) were measured in 42 chronic schizophrenic inpatients grouped according to their scores on the Brief Psychiatric Rating Scale (BPRS) and the Abnormal Involuntary Movement Scale (AIMS). Factor analysis was carried out on various combinations of variables. In patients with tardive dyskinesia (TD), cerebrospinal fluid DA, DOPAC, HVA, NA, and serum DBH were distributed into three factors; in patients without TD, these substances were assembled in only one factor. Cerebrospinal fluid DA, DOPAC, and HVA were dispersed in two factors in patients with severe positive symptoms versus one factor in subjects with mild productive signs. Factor structures diverged only when the variables listed above were included in the analysis. These findings support the hypothesis that both the dopaminergic and the noradrenergic system contribute to TD and that positive schizophrenic symptoms are associated with dopaminergic dysregulation.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Serotonin agonists cause parallel activation of the sympathoadrenomedullary system and the hypothalamo-pituitary-adrenocortical axis in conscious rats.

The effects of three potent serotonin (5-HT) agonists with different structures and 5-HT receptor binding profiles on sympathoadrenomedullary and hypothalamo-pituitary-adrenocortical axis functions were assessed in conscious, freely moving male Sprague-Dawley rats. The 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), the 5-HT1C agonist, m-chlorophenylpiperazine (m-CPP), and the 5-HT2/5-HT1C agonist, 1-(2,5-dimethoxy-4-iodophenyl)2-amino-propane (DOI), all produced marked dose-dependent increases in plasma epinephrine and ACTH concentrations. Both epinephrine and ACTH responses peaked at 10 min and showed strong positive correlations across all drugs and doses studied. Corticosterone increases showed a saturable response pattern and were close to the maximum level with a relatively small (approximately 2.5-fold) increase in plasma ACTH concentrations. Norepinephrine levels showed small dose-dependent increases after 8-OH-DPAT and m-CPP and decreases after DOI treatment. These results suggest that both the sympathoadrenomedullary system and the hypothalamo-pituitary-adrenocortical axis can be activated via 5-HT1 and 5-HT2 receptors and that these two systems may have common or similar regulatory mechanisms triggered by these stimuli.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Neurocirculatory regulation in cortisol-induced hypertension.

Effects of chronic glucocorticoid treatment on arterial baroreflex function and on cardiac beta- and vascular alpha-adrenoceptor-mediated responses were assessed in conscious, unrestrained Wistar-Kyoto rats. Cortisol (25 mg/kg/day) was administered for seven days using a subcutaneous reservoir pump. Arterial baroreflex-cardiac sensitivity was assessed by examining the relationship of the cardiac interbeat interval to the mean arterial blood pressure during phenylephrine or nitroprusside challenge; baroreflex-sympathoneural sensitivity was assessed from the ratio of the increase in the arterial norepinephrine concentration to the decrease in mean arterial pressure at 15 min during intravenous infusion of nitroprusside; cardiac beta-adrenoceptor-mediated responsiveness was estimated from heart rate responses to bolus-injected isoproterenol; and vascular alpha-adrenoceptor-mediated responsiveness was estimated from peak mean arterial pressure responses to bolus-injected phenylephrine. Cortisol treatment increased mean arterial pressure, decreased heart rate, and increased heart rate responses to isoproterenol, whereas baroreflex-vagal sensitivity, baroreflex-sympathoneural sensitivity, and pressor responses to phenylephrine were unaffected. The results indicate that hypertension due to chronic cortisol administration is not associated with decreased sensitivity of the baroreceptor-cardiac reflex. Baroreflex-sympathoneural sensitivity and alpha 1-adrenoceptor responsiveness also remain normal, whereas beta-adrenoceptor responsiveness is increased. The findings suggest that the pattern of neurocirculatory adjustment in glucocorticoid hypertension differs from that seen in other forms of hypertension.

Animals↗
PubMed1989

Different serotonin receptors mediate blood pressure, heart rate, plasma catecholamine and prolactin responses to m-chlorophenylpiperazine in conscious rats.

The serotonin (5-HT) agonist, m-chlorophenylpiperazine (m-CPP), has been shown to increase blood pressure (BP), heart rate (HR), plasma catecholamine and prolactin (PRL) concentrations and to cause hypoactivity in rodents. In the present study, we used selective 5-HT and adrenergic antagonists to study the involvement of different receptor subtypes on the effects of m-CPP in conscious, freely moving rats. Hypoactivity and PRL responses were blocked by pretreatment with metergoline but not by pretreatment with other antagonists. BP increases were antagonized by ritanserin (0.1, 0.63 and 2.0 mg/kg) and ketanserin; metergoline, xylamidine or prazosin pretreatment had only partial effects on BP responses. HR increases were antagonized by yohimbine, pindolol, ketanserin and by the two higher doses of ritanserin. After pretreatment with the two higher doses of ritanserin, m-CPP decreased markedly BP and HR. These decreases were prevented by metergoline pretreatment. Norepinephrine and epinephrine responses were dose-dependently attenuated by ritanserin; naloxone pretreatment attenuated epinephrine but not norepinephrine responses. These data suggest that hypoactivity, PRL responses, and cardiodepressive effects of m-CPP are mediated by 5-HT1 receptors. It is likely that the hypoactivity and PRL responses of m-CPP are mediated by 5-HT1B receptors, and the cardiodepressive effects by 5-HT1A receptors. Increases in BP appear to be primarily mediated by stimulation of 5-HT2 receptors. Both adrenergic and serotonergic mechanisms are involved in HR responses. The catecholamine responses to m-CPP appear to be partially mediated by 5-HT1C receptors and also by nonserotonergic mechanisms.

Animals↗
PubMed1988

Evidence for a direct peripheral effect of clonidine on the norepinephrine release in vivo in pithed rats.

To study the in vivo peripheral effects of clonidine on sympathetic neuronal function we measured, after different doses of clonidine, plasma norepinephrine (NE) and blood pressure (BP) responses during electric stimulation of sympathetic outflow in pithed male Sprague-Dawley rats. In this preparation, clonidine produced dose-dependent inhibition of the sympathetic stimulation-induced pressor and plasma NE responses. The dose of clonidine inhibiting the NE response by 50% (ID50) was 14.2 +/- 0.3 micrograms/kg i.v., while ID50 for the diastolic pressor response was 22.0 +/- 0.2 micrograms/kg i.v. Since clonidine did not alter the relationship between NE released into the plasma and the pressor responses, the entire effect of clonidine in decreasing the pressor response to sympathetic stimulation may be attributed to its presynaptic alpha 2-adrenoceptor-mediated inhibition of NE release.

Animals↗
PubMed1988

Effect of adjuvant reserpine treatment on catecholamine metabolism in schizophrenic patients under long-term neuroleptic treatment.

The clinical and biochemical effects of adjuvant reserpine treatment were investigated in 12 chronic schizophrenic patients on long-term neuroleptic medication. The global severity of the symptoms using the Brief Psychiatric Rating Scale did not change significantly in the whole group, however, a moderate decrease in positive symptoms (factors though disturbance, activation and hostile-suspiciousness) was observed for 5 patients. Cerebrospinal fluid (CSF) noradrenaline levels showed a consistent decrease, but other biochemical parameters (CSF dopamine metabolites, platelet MAO and serum dopamine-beta-hydroxylase activities) did not change significantly. The changes of clinical symptoms and biochemical parameters did not show any correlation.

Adjuvants, Pharmaceutic↗
PubMed1988

Sympathoadrenomedullary hyper-responsiveness to yohimbine in juvenile spontaneously hypertensive rats.

We examined responses of arterial plasma levels of the sympathetic neurotransmitter, norepinephrine (NE), of the adrenomedullary hormone, epinephrine (E), and of the intraneuronal NE metabolite, dihydroxyphenylglycol (DHPG), after intravenous administration of the alpha-2 adrenoceptor antagonist, yohimbine, in conscious, freely-moving juvenile (4-week old) or mature (12-week old) rats with spontaneous hypertension (SHRs) and their normotensive Wistar-Kyoto (WKY) controls. Mature SHRs and WKY rats had similar levels of plasma catechols at rest, whereas juvenile SHRs had significantly higher levels of NE (400 +/- 109 (SD) vs 233 +/- 62 pg/ml), E (371 +/- 168 vs 148 +/- 67 pg/ml), and DHPG (800 +/- 147 vs 589 +/- 54 pg/ml). After yohimbine, average responses of NE in the juvenile SHRs were more than 5 times, of E more than 7 times, and of DHPG more than 11 times those of the juvenile WKY rats. The responses of plasma catechols to yohimbine were not excessive in mature 12-week old SHRs. The results demonstrate increased sympathoadrenomedullary activity at rest and markedly enhanced sympathoadrenomedullary responsiveness to yohimbine in juvenile but not mature SHRs and are consistent with the hypothesis that early in the development of hypertension in this laboratory animal model there is an abnormal dependence on central neural alpha-2 adrenoceptors as part of an incompletely successful compensatory mechanism for limiting sympathetic outflow.

Adrenal Medulla↗
PubMed1988

The serotonin agonist, M-chlorophenylpiperazine, markedly increases levels of plasma catecholamines in the conscious rat.

Intravenous administration of the serotonin agonist, m-chlorophenylpiperazine (m-CPP), produced large, dose-dependent increases in epinephrine, norepinephrine and dopamine in plasma in normal, conscious rats. Elevations in the levels of epinephrine, norepinephrine and dopamine (10-fold, 5-fold and 2-fold, respectively) were markedly reduced in pithed and splanchnic denervated rats, suggesting that CNS mechanisms are primarily responsible for the effect of m-CPP on catecholamines in plasma. The serotonin antagonist, metergoline (0.5 mg/kg), decreased the responses of epinephrine and dopamine to m-CPP by 60-80% and also tended to decrease the response of norepinephrine. These findings are consistent with other studies reporting that stimulation of serotonergic receptors increases centrally-mediated sympathetic outflow and leads to increases in the concentrations of norepinephrine, epinephrine and dopamine in plasma.

Animals↗
PubMed1988

Diurnal variation in fentanyl-induced hormone responses and side effects.

The prolactin (PRL) and thyrotropin (TSH) secretory response to the opioid agonist fentanyl (0.1 mg IV) was investigated with serial blood sampling in ten healthy women at 9 AM and 9 PM on different days. In five subjects saline control trials were also performed. A repeated-measures analysis of variance yielded a highly significant effect of fentanyl administration both on PRL and TSH secretion. In every case there were elevated hormone responses in the evening, and more drug-related subjective symptoms were reported at this time than before noon. These findings indicate a diurnal variation of opioid responsiveness, with lower sensitivity in the morning.

Adult↗
PubMed1988

Sympathoadrenomedullary inhibition by chronic glucocorticoid treatment in conscious rats.

The effects of chronic glucocorticoid treatment on sympathoadrenomedullary function were assessed in conscious unrestrained Wistar-Kyoto rats. Cortisol (25 mg/kg.day), administered for 7 days using a sc reservoir pump, suppressed activity of the hypothalamo-pituitary-adrenocortical axis, as indicated by markedly decreased levels of corticotropin (ACTH) and corticosterone and decreased adrenal weight. Cortisol also decreased body weight and increased blood pressure to hypertensive levels without affecting plasma sodium or potassium. Basal levels of plasma epinephrine were markedly decreased, indicating suppression of adrenomedullary secretion. Plasma norepinephrine levels also were decreased, but to a smaller extent than epinephrine, and levels of dihydroxyphenylglycol, an intraneuronal metabolite of norepinephrine, were unaffected. Plasma catecholamine responses to nitroprusside-induced hypotension were not altered by cortisol. The results suggest that chronic cortisol treatment suppresses basal hypothalamo-pituitary-adrenocortical and basal adrenomedullary activity in conscious unrestrained rats without impairing reflexive activation of the sympathoadrenomedullary system.

Adrenal Medulla↗
PubMed1987

M-chlorophenylpiperazine increases blood pressure and heart rate in pithed and conscious rats.

In pithed rats, m-chlorophenylpiperazine (m-CPP) produced marked, dose-dependent (ED50 = 0.18 mumol) increases in mean arterial blood pressure which peaked within 1 minute and were sustained over 15 minutes. Two serotonin antagonists, metergoline and ritanserin, completely blocked the pressor responses to 2.5 mg/kg m-CPP in pithed adrenal demedullated rats, while alpha-adrenergic blockade by prazosin plus yohimbine was without effect, suggesting that the doubling in blood pressure produced by m-CPP was mediated via serotonin receptors within blood vessels. Somewhat smaller increases in blood pressure over baseline values were observed after m-CPP administration to conscious, freely moving rats. A small but statistically significant increase in heart rate peaked 5 minutes after m-CPP and also was blocked by metergoline but was only minimally affected by ritanserin or the prazosin-yohimbine combination. These results with m-CPP support other evidence for two or more separable effects of serotonergic agonists on the peripheral cardiovascular system.

Adrenal Medulla↗
PubMed1987

Serum dopamine-beta-hydroxylase activity and alcohol withdrawal symptoms.

Fifty male alcoholics had serum dopamine-beta-hydroxylase (DBH) activity, and serum prolactin (PRL) levels measured on the day of withdrawal, and 22 of them also on days 7 and 28 after it. The obtained values were related to the development of withdrawal symptoms. Treatment was begun with meprobamate on the first day of withdrawal, and from day 7 it was completed with disulfiram (250 and 500 mg/day, respectively). Serum DBH activity decreased significantly by day 7, however a further fall of it occurred by day 28 only in patients receiving high doses (500 mg) of disulfiram. PRL levels rose over the period of withdrawal which reached significance level on day 28. No correlation was found between serum DBH activity and the severity of withdrawal symptoms. Serum DBH activity did not differ from that of the healthy controls at either point of time, while serum PRL level was significantly elevated throughout the period of the study.

Adult↗