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Biomedical subjects

G Bagdy

Publications and source records attributed to G Bagdy.

At least 19 recordsLinked to original sources
PubMed2005

Sumatriptan causes parallel decrease in plasma calcitonin gene-related peptide (CGRP) concentration and migraine headache during nitroglycerin induced migraine attack.

Sumatriptan-induced changes in plasma calcitonin gene-related peptide (CGRP) concentration and headache intensity were investigated in 19 female migraineurs during nitroglycerin-induced migraine attack. Sumatriptan nasal spray was administered 120 min after the onset of the attack. Blood samples were obtained immediately before and 60 min after sumatriptan administration. In those subjects whose migraine attack improved considerably 60 min after the treatment the plasma CGRP concentration decreased significantly (P<0.05). In contrast, plasma CGRP concentration failed to change in patients whose headache did not improve. In addition, plasma CGRP concentrations showed significant positive correlations with the headache scores both 60 and 120 min after sumatriptan administration (P<0.05). According to our results plasma CGRP concentration decreases parallel to headache intensity during sumatriptan treatment and this decrease in CGRP predicts effectiveness of antimigraine drug therapy. This supports that one of the main effects of triptans is to decrease CGRP release.

Biomarkers↗
PubMed2002

Effect of sleep deprivation on spike-wave discharges in idiopathic generalised epilepsy: a 4 x 24 h continuous long term EEG monitoring study.

The aim of the study was to investigate the effect of sleep and sleep deprivation on spike-wave discharges (SWD) in an idiopathic generalised epileptic patient population by continuous long term cassette EEG monitoring for 4 x 24 h. In ten patients with idiopathic generalised epilepsy, showing SWD during awake state and in sleep as well, EEG and sleep polygraphy was recorded for 4 x 24 h. Sleep was deprived during the second 24 h. Awake state, NREM1, NREM2, NREM3+4 and REM sleep duration and number of SWD episodes were evaluated in 4 min intervals by visual scoring. For analysing the effect of 'day' and 'night', 'vigilance' and 'sleep deprivation' (SD) on the density variables multi-way ANOVAs were carried out in different designs. SWD densities for different vigilance states were not significantly different during 'day' and 'night' in 24 h without SD or rebound after SD. Sleep had an activating effect SWD densities being the highest during NREM1 and NREM2. There was an increase of SWD densities in all vigilance states after SD, but SWD densities remained the highest in NREM1 andNREM2. Our results support the view that sleep dependent rather than sleep independent mechanisms cause activation of SWD after SD in generalised epilepsy. We assume that fine graded vigilance fluctuations, that are more frequent after SD, have an essential role in SWD activation in superficial sleep or even in wakefulness.

Adult↗
PubMed2001

8-OH-DPAT and MK-801 affect epileptic activity independently of vigilance.

Vigilance and parallel occurrence of epileptic activity after administration of the 5-HT(1A) agonist 8-OH-DPAT and the NMDA receptor antagonist MK-801 were studied in the genetic absence epilepsy model WAG/Rij rats. Spike-wave discharges (SWD) were present predominantly in passive awake and light slow wave sleep (SWS1) either in control animals or after treatments. Injection of 8-OH-DPAT (20.0 microg/rat i.c.v.) caused marked increase and MK-801 (10.0 microg/rat i.c.v.) decrease in SWD densities, thus the ratios of SWD in passive awake and in SWS1. SWD densities of MK-801 plus 8-OH-DPAT in combination were similar to those of CSF+CSF treated control rats. Both 8-OH-DPAT and MK-801 transiently increased the duration of active awake, increased latency and decreased duration of rapid eye movement (REM) sleep. 8-OH-DPAT increased the amount of SWD despite the decrease in the duration of SWS1. MK-801 decreased the amount of SWD despite the lack of significant change in duration of passive awake or SWS1. Pre-treatment with MK-801 reversed 8-OH-DPAT- induced increase in duration of SWD without any effect on 8-OH-DPAT-induced changes in sleep parameters. Our studies provide evidence that 8-OH-DPAT-induced epileptic activity is independent of its effect on sleep, and that interaction of serotonergic and glutamatergic systems plays a role in the generation of SWD, but not in the regulation of vigilance and sleep.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2001

Rapid desensitization of 5-HT(1A) receptors in Fawn-Hooded rats after chronic fluoxetine treatment.

Anxiety, platelet serotonin (5-HT) content and functions of the 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) were measured in Sprague--Dawley (SD) and Fawn-Hooded (FH) rats, a strain with genetically impaired 5-HT storage and reuptake system and a putative model of depression and anxiety. In addition, the effects of 7 and 16 days treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine on 8-OH-DPAT-induced responses were studied. FH rats showed significantly higher anxiety in the social interaction test, and much lower platelet 5-HT content compared to SD rats. The efficacy of 8-OH-DPAT (15-120 microg/kg, i.v.) to induce lower lip retraction (an effect mediated by median raphe receptors) was increased in FH rats. In most FH but only a few SD rats a special neurological syndrome, clonic movement of the masseters and in-and-out movement of the eyeballs, was induced by 8-OH-DPAT, and this behaviour like other effects of 8-OH-DPAT, was completely blocked by pretreatment with the 5-HT(1A) receptor antagonist WAY-100635. In SD rats fluoxetine (10 mg/kg/day, i.p.) caused a moderate inhibition of 8-OH-DPAT-induced hypothermia, an effect mediated most likely by hypothalamic 5-HT(1A) receptors, (-19% and -40% after 7 and 16 days of fluoxetine, 24 h after the last injection, respectively). In FH rats fluoxetine caused a rapid and complete reduction in the 8-OH-DPAT-induced hypothermia (-65% and -91% after 7 and 16 days of fluoxetine, respectively). Fluoxetine caused no change in lower lip retraction but a reduction in the masseter-eyeball syndrome in both SD and FH rats. Our data provide evidence that in FH rats, median raphe 5-HT(1A) receptors are hypersensitive, and the hypothalamic 5-HT(1A) receptor desensitization, caused by SSRI antidepressants, is faster and more complete. These data support the notion that chronic treatment with SSRIs induces a desensitization of some 5-HT(1A) receptor populations, and impaired 5-HT storage and reuptake may accelerate this process.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2001

Anxiety-like effects induced by acute fluoxetine, sertraline or m-CPP treatment are reversed by pretreatment with the 5-HT2C receptor antagonist SB-242084 but not the 5-HT1A receptor antagonist WAY-100635.

The possible role of 5-HT1A and 5-HT2C receptors in the anxiety induced by fear, acute treatment with SSRI antidepressants or the 5-HT receptor agonist m-CPP were tested in the social interaction anxiety test in male Sprague-Dawley rats. Fluoxetine (2.5-10 mg/kg, i.p.), sertraline (15 mg/kg, i.p.) and m-CPP (0.5-2.0 mg/kg, i.p.) all had an anxiogenic-like profile (decrease in time of total social interaction and increase in self-grooming compared to vehicle) under low-light, familiar arena test conditions. All these effects were reversed by pretreatment with the highly subtype-selective 5-HT2C receptor antagonist, SB-242084 at doses of either 0.05 or 0.2 mg/kg, i.p. In contrast, the selective 5-HT1A receptor antagonist WAY-100635 (0.05 and 0.2 mg/kg, s.c.) failed to reverse SSRI-induced decrease in time of total social interaction, further, it augmented self-grooming response. SB-242084 (0.2 mg/kg) and WAY-100635 (0.05 and 0.2 mg/kg) reversed hypolocomotion caused by the SSRI antidepressants. SB-242084, tested alone against vehicle under high-light, unfamiliar arena test conditions associated with fear, caused significant anxiolysis at 0.2 mg/kg and higher doses. These results suggest that increased anxiety in rodents, and possibly, also in humans (e.g. agitation or jitteriness after SSRIs and panic after m-CPP), caused by acute administration of SSRI antidepressants or m-CPP, are mediated by activation of 5-HT2C receptors. Blockade of 5-HT1A autoreceptors may exacerbate certain acute adverse effects of SSRI antidepressants. Both 5-HT1A and 5-HT2C receptors are involved in the SSRI-induced decrease in locomotor activity. In addition, our studies confirm data that subtype-selective 5-HT2C receptor antagonists have strong anxiolytic actions.

Aminopyridines↗
PubMed2000

High social anxiety and low aggression in Fawn-Hooded rats.

The Fawn-Hooded (FH) rat strain, with well-documented changes in their serotonergic and noradrenergic systems, is a putative genetic model for some neuropsychiatric disorders like depression, alcohol abuse, and anxiety. Because social phobia frequently occurs in combination with these disorders and there are no social anxiety-related data in FH rats in the literature, we measured the behavior of FH rats in the social interaction test. In addition, the effects of the anxiogenic Serotonin-2C (5-HT2C) receptor agonist, m-chlorophenylpiperazine (m-CPP), were studied. Male FH, Wistar (W), and Sprague-Dawley (SD) rats were used in two different test conditions of the social interaction test: the high light, unfamiliar arena, associated with high anxiety, and the low light, familiar arena, associated with low anxiety-like behavior. All social behaviors were markedly diminished in FH rats that suggested higher anxiety in these animals. Total social interaction time was reduced by 60-70% in FH rats compared either to W or SD rats under high light, unfamiliar or low light, familiar conditions, respectively. Aggressive behavior was reduced at least by 85% in FH rats. Locomotor activity and exploratory behavior were only minimally, in most comparisons, not significantly affected in FH rats. Total social interaction time, aggression, and locomotor activity were decreased, and self-grooming increased by m-CPP (0.5 mg/kg, ip) in all three strains. m-CPP decreased total social interaction time thus, caused anxiety most efficiently in FH rats (reduced by 69%, 50%, and 55% in FH, W, and SD rats, respectively), but other effects of the drug were similar in the three strains. Our studies provide evidence that the FH rat strain may be a genetic model of social phobia or other anxiety disorders with impaired social behavior.

Aggression↗
PubMed2000

Blunted pituitary-adrenocortical stress response in adult rats following neonatal dexamethasone treatment.

Glucocorticoids have a prominent impact on the maturation of the stress-related neuroendocrine system and on the postnatal establishment of adaptive behaviour. The present study aimed at investigating the stress responsiveness of the hypothalamo-pituitary-adrenocortical (HPA) axis in young and adult rats after neonatal treatment with the synthetic glucocorticoid agonist, dexamethasone. Newborn male Wistar rats were injected s.c. with 1 microg/g dexamethasone on postnatal days 1, 3 and 5. Circulating adrenocorticotropic hormone (ACTH) and corticosterone concentrations were measured in the resting state and following a 30-min cold stress at the age of 10 days, as well as after a 30-min restraint stress at the age of 14 weeks. Also in adults, pituitary and adrenocortical hormone responsiveness was evaluated after i.v. administration of 2 microg/kg corticotropin releasing hormone (CRH). In addition, glucocorticoid (GR) and mineralocorticoid receptor (MR) binding capacities were assessed in the pituitaries of adult rats. The results showed that at day 10 basal ACTH concentration was elevated while the cold stress-evoked ACTH response was attenuated in the dexamethasone-treated rats. As adults, treated rats showed a suppressed elevation of both ACTH and corticosterone plasma concentrations in response to restraint, while basal hormonal concentrations were not altered. There was no difference in the magnitude of the CRH-induced elevation of ACTH and corticosterone concentrations initially; however, the dexamethasone-treated animals showed a prolonged secretion of both hormones. These animals also showed a selective decrease in pituitary GR binding capacity. Neonatal dexamethasone treatment strongly suppressed body weight gain, and adrenal and thymus weights in the early phase of postnatal development. By adulthood, the body and adrenal weights were normalized while thymus weight was greater than in controls. These findings indicate that neonatal dexamethasone treatment permanently alters HPA axis activity by reducing stress responses to cold and restraint probably through supra-pituitary actions, and by decreasing the effectiveness of feedback through a diminished GR binding in the pituitary.

Adrenal Glands↗
PubMed1999

Effects of acute and chronic fluoxetine treatment of CRH-induced anxiety.

The effects of acute and chronic fluoxetine treatment on anxiogenic effect of corticotropin-releasing hormone (CRH) were studied in the social interaction test in male Sprague-Dawley rats. Injection of CRH (100 ng, i.c.v.), fluoxetine (5 mg/kg, i.p.) or their combination had significant anxiogenic effects (decrease in total interaction time and increase in self-grooming) in the social interaction test. The effects of CRH and fluoxetine in combination were not additive. Fluoxetine, but not CRH significantly inhibited locomotor activity. After chronic fluoxetine treatment (5 mg/kg/day, 21 days) the acute anxiogenic effects of either CRH or fluoxetine were abolished. Our studies provide evidence for a 5-HT/CRH interaction in the regulation of anxiety.

Animals↗
PubMed1999

A serotonin-1A receptor agonist and an N-methyl-D-aspartate receptor antagonist oppose each others effects in a genetic rat epilepsy model.

The WAG/RIJ rats exhibit spontaneously occurring spike-wave discharges (SWD) accompanied by behavioural phenomena, with characteristics similar to the human absence type epilepsy. To study the mechanisms involved in this type of epileptiform activity we investigated the effects of the serotonin-1A (5-HT1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) and the N-methyl-D-aspartate (NMDA) receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine maleate (MK-801). Intracerebroventricular (i.c.v.) injection of 8-OH-DPAT caused marked, dose dependent increase, MK-801 a decrease in the cumulative duration and number of spike-wave discharges. Pretreatment with MK-801 (10 microg/rat i.c.v.) abolished the increase caused by 8-OH-DPAT (20 microg/rat i.c.v.), but the decrease in SWD to MK-801 was counterbalanced by 8-OH-DPAT. These data provide evidence for an interaction of glutamatergic and serotonergic mechanisms in the triggering and maintenance of epileptic activity in this genetic model of absence epilepsy.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1999

Anxiogenic effect of central CCK administration is attenuated by chronic fluoxetine or ipsapirone treatment.

The effect of chronic fluoxetine and ipsapirone treatment on the anxiogenic effect of centrally administered cholecystokinin (CCK) was studied in the social interaction test in male Sprague-Dawley rats. Intracerebroventricular injection of unsulfated CCK-8 significantly decreased total interaction time and locomotor activity and caused some increase in selfgrooming and a reduction in rearing behaviour in a familiar arena in low light conditions. The selective serotonin reuptake inhibitor antidepressant fluoxetine alone (5 mg/kg, i.p.) also had clear acute anxiogenic actions (decrease in total interaction time, locomotor activity, rearing, increase in selfgrooming) after single dosing, but all these effects were omitted after chronic (3 weeks) treatment. In contrast, a single injection of the 5-HT1A receptor partial agonist ipsapirone (5 mg/kg, i.p.) alone had only motor effects (decrease in selfgrooming and rearing), and these effects were preserved after chronic treatment. Chronic fluoxetine treatment (5 mg/kg per day, 3 weeks) abolished the effects of CCK-8 (1 nmol/rat, i.c.v.). Chronic treatment with ipsapirone (5 mg/kg per day, 3 weeks) partially attenuated the effects of CCK-8 (1 nmol/rat, i.c.v.). Our studies provide further evidence for a 5-HT/CCK interaction in the regulation of anxiety.

Animals↗
PubMed1998

The 5-HT1A agonist 8-OH-DPAT increases the number of spike-wave discharges in a genetic rat model of absence epilepsy.

The effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) on the epileptiform activity has been investigated in adult WAG/RIJ rats. Either intraperitoneal (0.1-0.5 mg/kg) or intracerebroventricular (2-20 microg/rat) administration of 8-OH-DPAT caused marked, dose-dependent increases in the number and mean cumulative duration of spike-wave discharges. These effects were attenuated by NAN-190, a 5-HT1A receptor antagonist. These data indicate that serotonergic system regulates the epileptiform activity in this genetic model of human absence epilepsy.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1998

Gender-dependent dissociation between oxytocin but not ACTH, cortisol or TSH responses to m-chlorophenylpiperazine in healthy subjects.

m-Chlorophenylpiperazine (m-CPP), a serotonin (5-HT) agonist with some selectivity for the 5-HT2C receptor subtype, which is widely used to examine 5-HT receptor function in human subjects, has been found to induce oxytocin and thyrotropin (TSH) responses in rodents. This study examined whether m-CPP had any effect on plasma oxytocin, TSH and aldosterone concentration in healthy volunteers using a double-blind, placebo-controlled crossover design. Plasma adrenocorticorticotropic hormone (ACTH) and cortisol responses, two generally accepted markers of m-CPP-induced 5-HT receptor activation, were measured in parallel. Male subjects (n=7) received placebo, 0.25 and 0.5 mg/kg oral m-CPP. In female subjects (n=5), the effects of placebo and 0.25 mg/kg m-CPP were studied. After placebo, given in the morning, ACTH, cortisol, TSH and aldosterone concentrations decreased over time. m-CPP 0.25 mg/kg avoided decreases in ACTH, cortisol and TSH concentrations; these responses were significant. At the dose of 0.5 mg/kg, m-CPP caused increase in ACTH, cortisol, TSH and aldosterone concentrations. Significant plasma oxytocin responses were found in female subjects only; thus this effect of m-CPP was statistically significantly gender dependent. Other responses to m-CPP were similar in male and female subjects. The present results suggest that there are clear differences, including dose and gender-dependent dissociations, among the 5-HT receptor agonist m-CPP-induced neuroendocrine responses.

Adrenocorticotropic Hormone↗
PubMed1997

Comparison of relative potencies of i.v. and i.c.v. administered 8-OH-DPAT gives evidence of different sites of action for hypothermia, lower lip retraction and tail flicks.

8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)-induced temperature reduction, lower lip retraction and tail flick responses are widely used models of 5-HT1A receptor function. To obtain information about the sites of receptors mediating these effects we measured these responses, parallel over wide dose ranges after intracerebroventricular (i.c.v., 0.6-67 micrograms/kg) and intravenous (i.v., 3-500 micrograms/kg) administration. Analysis of the dose-response curves provided evidence for a 9.8-fold ratio of the potency of 8-OH-DPAT following i.c.v. compared to i.v. administration on body temperature reduction (ED50 values are 5.1 and 50 micrograms/kg, after i.c.v and i.v. administration, respectively) and a 2.9-fold ratio in potency for lower lip retraction (ED50 values are 29 and 86 micrograms/kg, after i.c.v. and i.v. administration, respectively). 8-OH-DPAT was less potent in the induction of tail flicks than of the other responses and had a lower potency after i.c.v. than after i.v. administration (ED50 values, the first one extrapolated, are 526 and 246 micrograms/kg, after i.c.v. and i.v. administration, respectively). In addition, the i.c.v. ED50 for temperature reduction was significantly lower than those for lower lip retraction or tail flick responses. The relative potency, that is, the ratio of i.v. and i.c.v. ED50, was significantly higher for temperature reduction than for lower lip retraction or tail flick responses (ED50 i.v./ED50 i.c.v. values are 9.8, 2.9, and 0.47, respectively). These data provide evidence that distinct sites of action are involved in these models. Temperature reduction is mediated mainly by postsynaptic receptors in the close vicinity of the lateral ventricle. Receptors that mediate lower lip retraction are located more distantly in the brain, supporting previous evidence that they are somatodendritic autoreceptors, and receptors in the spinal cord are probably responsible for tail flick responses.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

Role of the hypothalamic paraventricular nucleus in 5-HT1A, 5-HT2A and 5-HT2C receptor-mediated oxytocin, prolactin and ACTH/corticosterone responses.

To test the hypothesis that the mechanisms of 5-HT1 and 5-HT2 receptor-mediated hormonal responses are different, we compared the effects of hypothalamic paraventricular nucleus (PVN) lesions on the ACTH/corticosterone, prolactin and oxytocin responses to the 5-HT1A agonist ipsapirone (1 and 2 mg/kg), the 5-HT2C agonist m-chlorophenylpiperazine (m-CPP, 0.6 mg/kg), which also binds to other 5-HT receptors with lower affinity, and the 5-HT2A/2C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 1 mg/kg) in chronically cannulated, freely moving male rats. Pharmacological characterization using antagonists with different affinity for 5-HT2A and 5-HT2C receptors revealed that DOI's responses were mediated mainly by 5-HT2A receptors and m-CPP's responses were almost exclusively mediated by 5-HT2C receptors. ACTH/corticosterone responses to ipsapirone, DOI and m-CPP were almost completely blocked after PVN lesions. Prolactin responses were significantly different in lesioned rats only after DOI and m-CPP challenges. Oxytocin responses to ipsapirone and DOI, but not m-CPP were markedly attenuated after PVN lesions. The present findings suggest that the PVN, or neural pathways close to it, mediate corticosterone and in some cases prolactin and oxytocin responses to selective stimulation of 5-HT1A, 5-HT2A, or 5-HT2C receptors.

Adrenocorticotropic Hormone↗
PubMed1996

Studies on the sites and mechanisms of 5-HT1A receptor-mediated in vivo actions.

In the first study the possible role of the hypothalamic paraventricular nucleus (PVN) in 5-HT1A receptor agonist-induced neuroendocrine responses was tested. Surgical lesions of the PVN completely blocked ACTH and corticosterone and markedly attenuated oxytocin but not prolactin responses to ipsapirone, providing evidence for a crucial role of the PVN in these responses. In the second study we have compared the effectiveness of intracerebroventricular and intravenous administration of 8-OH-DPAT in frequently used behavioural models of 5-HT1A receptor activation, namely lower lip retraction, body temperature and tail flick responses. We have found marked differences in the rates of effectiveness. We conclude that these models measure the activation of different subsets with clearly separate location of 5-HT1A receptors.

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