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Biomedical subjects

G N Pandey

Publications and source records attributed to G N Pandey.

At least 37 records · Page 2Linked to original sources
PubMed1997

Protein kinase C in the postmortem brain of teenage suicide victims.

Increased serotonin2A (5-HT2A) receptors have been reported in the postmortem brain of suicide victims. To examine if this increase is associated with the dysregulation of postreceptor sites in the signaling cascade, we determined [3H]phorbol dibutyrate (PDBU) binding to protein kinase C (PKC) in postmortem brain samples (Brodmann's areas 8 and 9) obtained from teenage suicide victims and control subjects. [3H]PDBU binding to PKC was determined in membranal and cytosolic fractions. We observed that Bmax of [3H]PDBU binding sites was significantly decreased in both membranal and cytosolic fractions in brain samples from Brodmann's areas 8-9 compared to matched controls. These results thus suggest that PKC may play a role in the pathophysiology of suicidal behavior.

Adolescent↗
PubMed1997

Psychotic exacerbations and enhanced vasopressin secretion in schizophrenic patients with hyponatremia and polydipsia.

BACKGROUND: For unclear reasons, life-threatening water intoxication often coincides with acute psychosis in polydipsic schizophrenic patients with chronic hyponatremia. In contrast, most polydipsic schizophrenic patients are normonatremic and never manifest hyponatremia. To explore whether the effect of acute psychosis on water balance differs in these 2 schizophrenic subgroups, we compared their responses to drug-induced psychotic exacerbations. METHODS: Matched polydipsic schizophrenic patients with (n = 6) and without (n = 8) hyponatremia were identified based on past and current indexes of fluid intake and hydration. A transient psychotic exacerbation was induced with an infusion of the psychotomimetic methylphenidate hydrochloride (0.5 mg/kg of body weight over a 60-second period). Antidiuretic hormone levels, subjective desire for water, and factors known to influence water balance were measured at 15-minute intervals for 2 hours. RESULTS: Except for the expected differences in plasma osmolality and sodium, basal measures were similar in the 2 groups. Following methylphenidate administration, antidiuretic hormone levels increased more in the hyponatremic patients (P < .02), despite their consistently lower plasma osmolality (P < .007). No known or putative antidiuretic hormone stimulus could account for this finding. Only basal positive psychotic symptoms (P < .09) and plasma sodium (P < .18) were even marginally associated with the peak antidiuretic hormone responses, but neither factor could explain the difference in the response by the 2 groups. CONCLUSION: Psychotic exacerbations are associated with enhanced antidiuretic hormone secretion, for unknown reasons, in schizophrenic patients with hyponatremia and polydipsia, thereby placing them at increased risk of life-threatening water intoxication.

Acute Disease↗
PubMed1997

Effects of subchronic administration of antidepressants and anxiolytics on levels of the alpha subunits of G proteins in the rat brain.

The aim of this study was to examine the effects of subchronic administration of psychoactive drugs on the alpha subunits of G proteins in the rat brain, and also to determine if different classes of psychoactive drugs share a common property, i.e., of altering levels of these proteins. For this purpose, we selected the psychoactive drugs desipramine and phenelzine (antidepressants), lithium (antimanic), alprazolam and buspirone (anxiolytics), and metachlorophenylpiperazine (anxiogenic). The levels of alpha subunits of G proteins (Gs, Gi 1/2, Gq/11) expressed in cortical, hippocampal, and cerebellar brain regions were studied by the Western blot technique. We observed that subchronic treatment with lithium significantly decreased, and with phenelzine significantly increased levels of Gi 1/2 alpha protein in the cortex and the hippocampus. On the other hand, buspirone significantly decreased levels of Gi 1/2 alpha protein only in the cerebellum. Other psychoactive drugs, however, namely desipramine, meta-chlorophenylpiperazine, and alprazolam, did not alter levels of Gs, Gi 1/2, or Gq/11 alpha proteins in any of the brain regions studied. Since other studies have shown the involvement of G proteins in the mechanism of action of psychoactive drugs, our results demonstrate that expressed protein levels of the alpha subunit of G proteins are not altered by all the psychoactive drugs.

Animals↗
PubMed1996

Modulation of serotonin2A/2C receptors and these receptor-linked phosphoinositide system by ethanol.

Studies related to 5-HT2A/2C receptors and these receptor-linked phosphoinositide (PI) system in the rat brain during chronic ethanol treatment and withdrawal are discussed. Chronic ethanol treatment (60 days) has no effect on 5-HT2A/2C receptors in the cortex and the hippocampus but significantly decreased 5-HT-stimulated PI hydrolysis in the rat cortex. On the other hand, chronic ethanol treatment (60 days) significantly increased 5-HT2C receptors and 5-HT-stimulated PI hydrolysis in the rat choroid plexus. Ethanol withdrawal (24 h) after chronic ethanol consumption (15 days) results in the down-regulation of 5-HT2A receptors and in a decrease in 5-HT-stimulated PI hydrolysis in the rat cortex. Taken together, these results, along with other reports in the literature, suggest that 5-HT2A/2C receptors or their function are altered during chronic ethanol consumption and withdrawal. Further studies are needed to explore the role of 5-HT2A/2C receptors and the PI signal transduction system in the development of ethanol withdrawal symptoms after chronic ethanol consumption.

Alcoholism↗
PubMed1996

Alterations in serotonin1B (5HT1B) receptor subtypes in the brain of ethanol-treated rats.

The effects of acute or chronic ethanol treatment and of withdrawal (24 h) after chronic ethanol treatment on 5HT1B receptor subtypes in different regions of the rat brain were investigated. Male Sprague-Dawley rats were fed the ethanol (9% v/v)-containing Lieber-DeCarli liquid diet or the control liquid diet for 1 day in the acute study and for 15 days in the chronic study. The ethanol-withdrawn group received the Lieber-DeCarli control liquid diet instead of the ethanol diet on the 15th night. Ethanol-withdrawn rats after 15 days of ethanol treatment were rated for withdrawal symptoms (e.g. hyperactivity, piloerection, squealing, and enhanced startle reflex) and were found to exhibit such symptoms after 24 h of ethanol withdrawal. The rats were decapitated, and cortices, cerebelli, striata, and hippocampi were separated for measurement of 5HT1B receptors by receptor binding techniques using 125I-cyanopindolol (CYP) as the ligand. It was observed that acute ethanol treatment had no significant effect on the maximum number of binding sites (Bmax) or the apparent dissociation constant (KD) of 5HT1B receptor binding sites in the various brain regions. On the other hand, chronic ethanol treatment produced a significant increase in Bmax of 125I-CYP binding to 5HT1B receptors in the rat cortex and hippocampus, which remained increased after 24 h of ethanol withdrawal. In contrast, in the striatum and the cerebellum of chronic ethanol-treated and withdrawn rats, the 5HT1B binding parameters (Bmax and KD) were unchanged. These results suggest the possible involvement of cortical and hippocampal 5HT1B receptors in ethanol dependence.

Animals↗
PubMed1995

Platelet serotonin-2A receptors: a potential biological marker for suicidal behavior.

OBJECTIVE: Abnormalities in the serotonergic system have been implicated in suicidal behavior. Higher numbers of serotonin-2 (5-HT2) receptors have been reported in the post-mortem brain of suicide victims. In order to further examine the role of 5-HT2A receptors in suicidal behavior, the authors studied 5-HT2A receptors in platelets of suicidal and nonsuicidal patients as well as normal comparison subjects. METHOD: 5-HT2A receptor levels were determined by using [125I]LSD as a radioligand in platelets obtained from hospitalized psychiatric patients (N = 131) and nonhospitalized normal comparison subjects (N = 40) during a drug-free baseline period. Patients were diagnosed according to DSM-III-R criteria, and suicidal behavior was identified by using the Hamilton Depression Rating Scale. RESULTS: The mean maximum number of binding sites (Bmax) of platelet 5-HT2A receptors for all suicidal patients was significantly higher than for nonsuicidal patients or normal comparison subjects. This significant difference remained when subgroups of suicidal patients with depression, schizophrenia, schizoaffective disorder, or bipolar illness were compared to the other two subject groups. The higher number of platelet 5-HT2A receptors in suicidal patients was independent of diagnosis. While there was no significant difference in Bmax between patients with serious suicidal ideation and those who made suicidal attempts, both groups had significantly higher Bmax than normal comparison subjects. CONCLUSIONS: The observed higher number of platelet 5-HT2A receptors in suicidal patients is independent of diagnosis and appears to be associated with both the brain and the platelets of suicidal patients. These results thus suggest the potential usefulness of platelet 5-HT2A receptors as a biological marker for identifying suicide-prone patients.

Adult↗
PubMed1995

Phosphoinositide system-linked serotonin receptor subtypes and their pharmacological properties and clinical correlates.

Serotonergic neurotransmission represents a complex mechanism involving pre- and post-synaptic events and distinct 5-HT receptor subtypes. Serotonin (5-HT) receptors have been classified into several categories, and they are termed as 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 type receptors. 5-HT1 receptors have been further subdivided into 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E and 5-HT1F. 5-HT2 receptors have been divided into 5-HT2A, 5-HT2B and 5-HT2C receptors. All 5-HT2 receptor subtypes are linked to the multifunctional phosphoinositide (PI) signalling system. 5-HT3 receptors are considered ion-gated receptors and are also linked to the PI signalling system by an unknown mechanism. The 5-HT2A receptor subtype is the most widely studied of the 5-HT receptors in psychiatric disorders (for example, suicide, depression and schizophrenia) as well as in relation to the mechanism of action of antidepressant drugs. The roles of 5-HT2C and 5-HT3 receptors in psychiatric disorders are less clear. These 5-HT receptors also play an important role in alcoholism. It has been shown that 5-HT2A, 5-HT2C and 5-HT3 antagonists cause attenuation of alcohol intake in animals and humans. However, the exact mechanisms are unknown. The recent cloning of the cDNAs for 5-HT2A, 5-HT2C and 5-HT3 receptors provides the opportunity to explore the molecular mechanisms responsible for the alterations in these receptors during illness as well as pharmacotherapy. This review article will focus on the current research into the pharmacological properties, molecular biology, and clinical correlates of 5-HT2A, 5-HT2C and 5-HT3 receptors.

Alcoholism↗
PubMed1994

Peripheral benzodiazepine receptors are decreased during cocaine withdrawal in humans.

In the present study, homovanillic acid in plasma (pHVA) and benzodiazepine receptors (3H-PK11195 binding) in neutrophil membranes were determined in blood obtained from cocaine-dependent (DSM-III-R) adult male inpatients at baseline-(within 72 hr of last cocaine use) and after 3 weeks of cocaine abstinence, and normal controls. The mean (+/- SEM) pHVA at baseline (10.3 ng/ml +/- 1.1) was similar to normals and did not change after 3 weeks of cocaine abstinence. Similarly, the binding indices of benzodiazepine receptors in cocaine-dependent subjects as a group were not significantly different than in normal controls. In 10 cocaine-dependent subjects, however, where both blood samples were available, the number of 3H-PK11195 binding sites was significantly (p < 0.05) decreased after 3 weeks of cocaine abstinence (mean +/- sem: Bmax = 6371 +/- 657 fmol/mg protein) compared with baseline (Bmax = 7553 +/- 925 fmol/mg protein), although there were no differences in the binding affinity (mean +/- sem: KD = 8.6 +/- 1.2 nmol/L after 3 weeks of abstinence compared with 8.1 +/- 1.0 nmol/L at baseline). These preliminary results suggest that peripheral benzodiazepine receptors may play an important role in the pathophysiology of cocaine withdrawal in cocaine-dependent human subjects.

Adult↗
PubMed1993

Modulation of 5-HT1C receptors and phosphoinositide system by ethanol consumption in rat brain and choroid plexus.

The effect of chronic ethanol consumption (60 days) on 5-HT1C receptors as measured by [3H]mesulergine binding in the hippocampus, cortex, and choroid plexus of rats was investigated. The 5-HT1C receptor-mediated phosphoinositide hydrolysis in rat choroid plexus was also investigated. It was observed that chronic ethanol treatment significantly increased the 5-HT-stimulated [3H]inositol 1-phosphate ([3H]IP1) formation, as well as the density (Bmax) of 5-HT1C receptors without causing a significant change in affinity (KD) of [3H]mesulergine binding in rat choroid plexus. It was also observed that chronic ethanol consumption had no significant effect on the Bmax or KD of 5-HT1C receptor binding sites in the hippocampus and cortex brain regions of rats. These results thus suggest that chronic ethanol consumption causes an up-regulation of both 5-HT1C receptors and 5-HT1C receptor-mediated phosphoinositide hydrolysis in rat choroid plexus but has no significant effects on the 5-HT1C receptors in brain. These results also suggest that 5-HT1C receptors and their functional response may be involved in the pathogenesis of alcohol dependence.

Animals↗
PubMed1993

Platelet serotonin-2 receptors in obsessive-compulsive disorder.

To examine the role of serotonin-2 (5-HT2) receptors in obsessive-compulsive disorder (OCD), we studied 5-HT2 receptors in platelets obtained from patients with OCD (n = 20) during a drug free baseline period, as well as in normal control subjects (n = 25). The maximum number of binding sites (Bmax) and the apparent dissociation constant (Kd) of 5-HT2 receptors were determined by receptor binding techniques using 125I-lysergic acid diethylamide (LSD) as radioligand. We observed that the mean Bmax of 125I-LSD binding in platelets of patients with OCD was not significantly different when compared with normal control subjects. There was also no significant difference in Kd values between patients with OCD and normal control subjects. To examine whether the baseline 5-HT2 receptors are related to the severity of illness, we determined the relationships of the baseline Bmax and Kd with baseline scores of the Hamilton Depression Rating Scale (HDRS), the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and the National Institute of Mental Health (NIMH) Obsessive-Compulsive scale (GOCS). We found no significant correlation between baseline Bmax and Kd with the baseline HDRS, Y-BOCS, or NIMH-GOCS scores. Our results do not indicate abnormal 5-HT2 receptors in platelets of patients with OCD.

Adult↗
PubMed1993

Beta-receptor responsiveness after desipramine treatment.

To examine whether a tricyclic antidepressant affects the functional response to a beta-receptor agonist in man, the response of heart rate, blood pressure, and plasma cAMP to isoproterenol was measured in 14 normal controls taking 75 mg desipramine daily. Desipramine significantly increased the bolus dose of isoproterenol needed to increase heart rate by 25 bpm at 14-30 days but not at 3-8 days. During infusions of isoproterenol, the increase in systolic blood pressure was blunted at both 3-8 days and 14-30 days, while the decrease in diastolic blood pressure was unaffected. Blood pressure findings were not affected by preadministration of bethanechol. In ten controls, isoproterenol infusions increased plasma cAMP, but this was unaffected by desipramine treatment. These findings suggest a decrease in the functional response of beta 1, but not beta 2, receptors after treatment with desipramine.

Adult↗
PubMed1993

Platelet serotonin-2 receptors in schizophrenia: effects of illness and neuroleptic treatment.

To examine the role of serotonin2 (5-hydroxytryptamine2, 5-HT2) receptors in schizophrenia, we determined the binding indices of 5-HT2 receptors using 125I-lysergic acid diethylamide (LSD) as the radioligand in platelets obtained from 40 normal control subjects and 42 drug-free schizophrenic patients. We also examined the effect of neuroleptic drug treatment on the binding parameters (Bmax and Kd) of 5-HT2 receptors in platelets of schizophrenic patients. We observed that the Bmax of 125I-LSD binding in platelets of schizophrenic patients was significantly higher than in platelets of normal subjects. There was no significant difference, however, between the Kd of 125I-LSD binding in platelets of schizophrenic patients and normal control subjects. Furthermore, we found no correlation between Brief Psychiatric Rating Scale scores and either Bmax or Kd of 125I-LSD binding at the end of the drug washout period. We also observed that neither treatment with haloperidol nor treatment with thiothixine caused significant changes in Bmax and Kd of 125I-LSD binding in platelets of schizophrenic patients. However, both fluphenazine and trifluoperazine did significantly increase the Bmax of 125I-LSD binding without any significant change in the Kd values in platelets of schizophrenic patients. Our results thus suggest that platelet 5-HT2 receptors are increased in schizophrenia and that chronic treatment with fluphenazine and trifluoperazine, but not haloperidol or thiothixine, further increases the 5-HT2 receptor binding sites in platelets of schizophrenic patients.

Adult↗
PubMed1992

Effect of electroconvulsive shock on 5-HT2 and alpha 1-adrenoceptors and phosphoinositide signalling system in rat brain.

We studied the effect of repeated administration of electroconvulsive shock (ECS) on alpha 1-adrenoceptor subtype (alpha 1A and alpha 1B) and 5-HT2 (serotonin-2) receptors and receptor-mediated phosphoinositide (PI) hydrolysis in rat cerebral cortex. We observed that repeated administration with ECS significantly increased the density of 5-HT2 receptors, as labeled by [3H]ketanserin, as well as 5-HT-stimulated [3H]inositol-1-phosphate ([3H]IP1) in rat cerebral cortex. We also observed that repeated ECS administration caused a significant increase in the number of alpha 1-adrenoceptors and the alpha 1B-adrenoceptor subtype as measured by (+/-)-beta-([125I]iodo-4-hydroxyphenyl)-ethyl-aminomethyl-tetralone binding. However, it had no significant effects on norepinephrine (NE)-stimulated [3H]IP1 formation or alpha 1A-adrenoceptor subtype. These results thus suggest that up-regulation of 5-HT2 receptors after administration with ECS is associated with increased 5-HT-stimulated [3H]IP1 formation. The lack of effects on NE-stimulated PI turnover in ECS treated rats may be due to its lack of effect on the alpha 1A-adrenoceptor subtype.

Animals↗
PubMed1992

Monoamine oxidase and cortisol response in depression and schizophrenia.

The relationship between hypothalamic-pituitary-adrenal (HPA) axis function and platelet monoamine oxidase (MAO) activity was examined in drug-free depressed (n = 32) and schizophrenic (n = 36) inpatients. HPA function was measured by determining plasma cortisol levels at 8:30 a.m. and 11 p.m. before, and 8:30 a.m., 4 p.m., and 11 p.m. after administration of 1 mg of dexamethasone (DEX). There was a significant correlation between platelet MAO activity and all post-DEX cortisol levels (8:30 a.m., 4 a.m., and 11 p.m.) in depressed patients, and MAO activity and pre-DEX cortisol levels (11 p.m.) in schizophrenic patients. MAO activity was significantly higher in depressed DST nonsuppressors than in suppressors, and there were more DST nonsuppressors in high-MAO groups as compared with low-MAO groups. Our results thus suggest a strong relationship between platelet MAO activity and HPA function in depressed patients. These biochemical markers are potentially useful in the identification of biochemically and clinically homogeneous subgroups of depressed patients.

Adult↗
PubMed1992

Effect of ethanol administration and withdrawal on serotonin receptor subtypes and receptor-mediated phosphoinositide hydrolysis in rat brain.

The effect of short-term (15 days) and long-term (60 days) ethanol treatment and withdrawal on agonist-stimulated phosphoinositide (Pl) hydrolysis, serotonin receptor subtypes (5HT1A and 5HT2), and alpha 1-adrenergic receptors were studied in rat cerebral cortex. Short-term ethanol treatment had no significant effect on serotonin (5HT), norepinephrine (NE), and calcium ionophore (A23187)-stimulated [3H]-inositol-1-phosphate ([3H]-IP1) formation and 5-HT2 receptors as measured by 125I-lysergic acid diethylamide (125I-LSD) binding, in rat cerebral cortex. However, 15 days of ethanol treatment, followed by 24 hr of withdrawal resulted in a decrease in Bmax of 125I-LSD binding without significant change in KD, as well as a decrease in 5HT-stimulated [3H]-IP1 formation in rat cerebral cortex. 5HT1A and alpha 1-adrenergic receptors were determined by using [3H]-8-hydroxy-2-(di-N-propylamino)tetralin and [3H]-prazosin as radioligand, respectively. We also observed that long-term ethanol treatment had no significant effect on Bmax and KD of 5HT2, 5HT1A, and alpha 1-adrenergic receptors, as well as NE and A23187-stimulated [3H]-IP1 formation, but significantly decreased the 5HT-stimulated [3H]-IP1 formation in rat cerebral cortex. It is possible that a decrease in 5HT-induced PI turnover after long-term ethanol exposure may be due to a decrease in coupling of 5HT2 receptors to G protein or PLC enzyme, whereas the decrease in 5HT-induced PI turnover after withdrawal may be due to a decrease in functional 5HT2 receptor number.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Similar effects of treatment with desipramine and electroconvulsive shock on 5-hydroxytryptamine1A receptors in rat brain.

The effect of chronic and acute treatment with desipramine (DMI) and electroconvulsive shock (ECS) on 5-hydroxytryptamine1A (5-HT1A) receptors was determined in the cortex and the hippocampus brain regions of rats. We observed that chronic treatment with both DMI and ECS significantly decreased 5-HT1A receptors, as determined by [3H]8-hydroxy-2-(di-n-propylamino)tetralin [( 3H]8-OH-DPAT) binding, in the cortex but not in the hippocampus. Acute treatment with DMI or ECS did not significantly alter the 5-HT1A receptors in the cortex. Neither chronic nor acute treatment influenced KD of [3H]8-OH-DPAT binding in the cortex or hippocampus. These results thus suggest that in contrast to the effects on 5-HT2 receptors, tricyclics as well as ECS produce similar effects on 5-HT1A receptors, suggesting that this site may represent a common site of action for antidepressant treatment.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Behavioral and biochemical effects of methylphenidate in schizophrenic and nonschizophrenic patients.

The authors examined the specific behavioral and biochemical effects of intravenous methylphenidate in a sample of schizophrenic and nonschizophrenic patients. Twenty drug-free patients participated in a double-blind, placebo randomized study of methylphenidate, with multiple samples of plasma homovanillic acid (HVA) and serum growth hormone (GH) obtained during the infusion procedure. Methylphenidate caused a significant increase in positive symptoms that was relatively specific to the schizophrenic patients and was evident even in those with otherwise dormant symptomatology. When behavioral response was correlated with the biochemical responses (i.e., changes in plasma HVA and GH), there was a significant positive relationship between the increase in the BPRS-positive symptoms as well as the hostility/suspiciousness factor, and the increase in GH. These results suggest that the expression of psychotic symptoms may be associated with increased dopaminergic postsynaptic sensitivity, although the nonspecific nature of methylphenidate's actions discourages a stronger interpretation of the results.

Adult↗