Biomedical subjects

A Yuwiler

Publications and source records attributed to A Yuwiler.

At least 19 recordsLinked to original sources

PubMed1992

Effects of acute and chronic fenfluramine on self-stimulation and its facilitation by amphetamine.

DL-Fenfluramine (20 mg/kg) releasing serotonin and amphetamine (2 mg/kg) releasing dopamine were given to adult rats trained to bar press for electrical stimulation to the medial forebrain bundle. Amphetamine treatment enhanced lever-pressing for 1-2 h. A single fenfluramine treatment rapidly suppressed self-stimulation with slow recovery in 5-7 days to a rate below the initial basal rate. A second treatment a week later again suppressed response rate and rates returned to a still lower baseline. Combined fenfluramine-amphetamine treatment at this time transiently abolished lever pressing for 1-3 h followed by 9-11 h of enhanced responding. The serotonin antagonist, ketanserine (0.1 mg/kg), but not cyproheptadine (0.1 mg/kg i.p.), partially protected against the effects of fenfluramine. The serotonin agonist, quipazine (0.5 mg/kg), but not dimethoxyiodophenylisopropylamine (DOI) (2.2 mg/kg), partially substituted for fenfluramine in the combined treatment. Fenfluramine markedly depleted serotonin and 5-hydroxyindoleacetic acid in frontal cortex, hippocampus, and caudate putamen. Ventral and midline midbrain regions were less affected. Combined fenfluramine and amphetamine treatment elevated dopamine levels in frontal cortex, hippocampus and caudate-putamen, but not in midbrain. These findings support a serotonin-dopamine interaction in self-stimulation behavior and suggest that repeated fenfluramine treatment results in chronic low level serotonergic stimulation and diminished serotonin storage capacity.

Amphetamine↗

PubMed1992

Hyperserotoninemia and antiserotonin antibodies in autism and other disorders.

This study examined the linkage between elevated blood serotonin in autism and the presence of circulating autoantibodies against the serotonin 5HT1A receptor. Information was also obtained on the diagnostic and receptor specificity of these autoantibodies. Blood serotonin was measured as was inhibition of serotonin binding to human cortical membranes by antibody-rich fractions of blood from controls and from patients with childhood autism, schizophrenia, obsessive-compulsive disorder, Tourette's, and multiple sclerosis. The results showed elevated blood serotonin was not closely related to inhibition of serotonin binding by antibody-rich blood fractions. Inhibition of binding was highest for patients with multiple sclerosis and was not specific to the 5HT1A receptor as currently defined. Although inhibition was not specific to autism, the data were insufficient to establish if people with autism differed from normal controls on this measure.

Adolescent↗

PubMed1992

Plasma catecholamines and social behavior in male vervet monkeys (Cercopithecus aethiops sabaeus).

Many investigations in humans indicate that epinephrine, norepinephrine and their ratio may correlate with such traits as social competence, academic achievement, and aggression. However, the socioeconomic, dietary, and environmental confounds accompanying most human studies complicate their interpretation. Social status, aggression, and other social behaviors can be reliably assessed in nonhuman primates under conditions controlling for crucial environmental factors. If interpretation of human studies is correct, dominant and subordinate male vervet monkeys should exhibit distinctive patterns of catecholamine secretion. To test this possibility, seventeen adult male monkeys living in six stable social groups were observed for 6 months. Based on their success in agonistic events, subjects were categorized as dominant or subordinate. Alpha scores were calculated from empirically derived factors to provide a noncategorical measure of dominant behavioral style. Plasma epinephrine and norepinephrine samples obtained from anesthetized subjects did not differ between dominant and subordinate males. Alpha scores, however, distinguished high from low norepinephrine/epinephrine ratio groups. These findings are consistent with studies in humans linking high epinephrine, low norepinephrine, and social competence.

Animals↗

PubMed1992

Chromosomal aberrations in a patient with severe psychopathology.

The case of a female patient showing aggressive, compulsive, destructive behaviour, ritualistic faecal smearing, and hyperactivity is presented. The behaviour is long standing, therapy-resistant, and its aetiology is unknown, although it is seemingly associated with chromosomal abnormalities secondary to abnormal plasma factors.

Abnormalities, Multiple↗

PubMed1992

Individual differences in basal cisternal cerebrospinal fluid 5-HIAA and HVA in monkeys. The effects of gender, age, physical characteristics, and matrilineal influences.

We examined the effects of gender, age, weight, length, body shape (ectomorphy), and matrilineal influences on cisternal cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA) and homovanillic acid (HVA) in 78 socially living adult and adolescent vervet monkeys. CSF 5-HIAA and the 5-HIAA:HVA ratio were higher (by 27% and 18%, respectively) in females. In both sexes, CSF 5-HIAA and the 5-HIAA:HVA ratio increased with age. Neither weight nor length were independently related to CSF 5-HIAA or HVA; however, shape correlated with CSF 5-HIAA and HVA in males (higher in thin, long subjects). Male offspring had CSF 5-HIAA concentrations and 5-HIAA:HVA ratios that were significantly closer to their mothers than did age-matched, maternally unrelated males. Repeated measures of CSF 5-HIAA and HVA in another 22 males living in unvarying settings showed that individual differences in these measures persisted over time. The data underscore the impact of gender, age, and matrilineal relationships on individual differences in CSF monoamine metabolites and highlight the importance of controlling for age and gender in neuropharmacological investigations of clinical populations.

Aging↗

PubMed1992

Age, alcoholism and depression are associated with low levels of urinary melatonin.

Two normal control populations, separated by 8,000 miles and 24 degrees of latitude, had similar six-month mean values for overnight urinary melatonin concentrations. These values were significantly higher than six-month values for depressed subjects and abstinent alcoholic subjects, while the means for the two clinical populations were similar. Age and urinary melatonin concentration in the control and clinical populations were inversely related, but the slopes of the linear regression equations were ten times steeper for the control populations than for the clinical populations. Differences in age and sex distributions accounted for some of the differences in values between controls and the clinical populations, although controls still differed from the clinical populations, even after sex and age were factored out. The disparate slopes for age and melatonin concentrations may contribute to some of the conflicting findings of studies comparing populations of different ages. The total melatonin content in the samples from alcoholic subjects, but not the depressed subjects, was lower than that for controls. The difference in the urinary melatonin concentration between the controls and the two patient groups was not accounted for by difference in duration of urine collection period, hours of sleep or body weight.

Adult↗

PubMed1991

Serotonergic mechanisms promote dominance acquisition in adult male vervet monkeys.

In a counter-balanced, cross-over study, we examined the contributions of serotonergic systems to the acquisition of social dominance in adult male vervet monkeys. Subjects were members of 12 social groups, each containing 3 adult males, at least 3 adult females, and their offspring. Animals were observed in 5 intervals including a first baseline, a first experimental, a second baseline, a second experimental, and a third baseline period. At the end of the first baseline period, the dominant male was removed from each group. In each group, one of the two remaining subordinate males was selected at random for treatment and during the first experimental period, 6 of the 12 treated males received drugs that enhanced serotonergic activity (3 were given tryptophan 40 mg/kg/day and 3 fluoxetine 2 mg/kg/day). The other 6 treated males received drugs that reduced serotonergic function (3 were given fenfluramine 2 mg/kg/day and 3 cyproheptadine 60 micrograms/kg/day). At the end of the first experimental period, the original dominant male was returned to his group and the second baseline period began. In all instances, the originally dominant male regained his dominant position. The second experimental period began with the dominant male again being removed and, the 12 treated males were given the treatment they had not received in the first experimental period. At the start of the third 12-week baseline period, the original dominant male was returned to his group and resumed his dominant status. When the 12 treated subjects received tryptophan or fluoxetine, they became dominant in all instances. When they received fenfluramine or cyproheptadine, their vehicle-treated cage mates became dominant. The sequence of the behavioral changes shown by the treated males as they acquired dominance status paralleled those seen in naturalistic conditions. These observations support the distinction between dominance and aggression and strongly suggest that when hierarchical relationships are uncertain, serotonergic mechanisms may mediate the behaviors which permit a male to attain high dominance status.

Aggression↗

PubMed1991

Whole blood serotonin in juvenile obsessive-compulsive disorder.

Whole blood serotonin (5-HT) concentration was assessed in 16 children and adolescents with severe obsessive-compulsive disorder (OCD) and in 14 normal adolescent controls. There was no difference in blood 5-HT content between the OCD patients and the normal controls. However, the OCD patients with a family history of OCD had significantly higher blood 5-HT levels than did either the OCD patients without a family history of OCD or the normal controls. Blood 5-HT content was not associated with a history of major depressive disorder or chronic tic disorder. These preliminary results suggest that studies of serotonergic functioning in OCD may need to control for family history of OCD and that blood 5-HT may be a useful biochemical measure in family-genetic studies of OCD.

Adolescent↗

PubMed1991

Fenfluramine effects on serotonergic measures in vervet monkeys.

Chronic fenfluramine treatment reduced whole blood serotonin and CSF 5-hydroxyindoleacetic acid, but increased aggressive and locomotor behavior, in adult male vervet monkeys (Cercopithecus aethiops sabaeus). Following a drug-free washout period to monitor the drug recovery course, we initiated a second period of fenfluramine treatment in the same animals. When whole blood serotonin concentrations were reduced by about 40% from predrug baseline levels, we examined 11 cortical and subcortical brain regions for their content of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, norepinephrine, and dopamine. We observed correspondence between the reduction in whole blood serotonin and the reduction in brain 5-hydroxytryptamine. Similarly, there was a correspondence between the reduced 5-hydroxyindoleacetic acid levels observed in CSF and brain. No alterations were noted in the concentrations of norepinephrine or dopamine. These observations suggest that the behavioral effects observed in monkeys after chronic fenfluramine treatment result from reduced central serotonin.

Animals↗

PubMed1991

The effects of benzodiazepines on basal and isoproterenol-stimulated N-acetyltransferase activity by the rat pineal gland, in vivo and in vitro.

The present study examined the effects of "peripheral," "central," and "mixed" benzodiazepine agonists and antagonists on the nocturnal rise in rat pineal NAT activity in vivo and the isoproterenol-stimulated NAT activity of pineals in organ culture. Administration of the central agonist clonazepam or the mixed agonist-antagonist diazepam, 4 hr after dark, at a dose of 25 mg/kg each, inhibited nocturnally elevated NAT 20 min later, while this same dose of the peripheral agonist RO 54864 elevated NAT activity. In a second study these agents were administered in vivo 1 hr before dark, at a dose of 3, 10, or 25 mg/kg i.p. and tested 4 hr after dark for in vitro rat pineal NAT activity. None of these agents affected NAT activity at the 3- or 10-mg/kg dose, but RO 54864 25 mg/kg did induce elevated activity. In a third study, all of these agents prolonged the time period for NAT induction by isoproterenol in rat pineals cultured for 48 hr before stimulation. The data suggests that benzodiazepine stimulation of NAT activity in vitro is not specific to "central" or "peripheral" benzodiazepine receptors and that inhibition of melatonin production in vivo occurs either at some step before NAT induction or is involved with the inhibition of pineal HIOMT activity.

Analysis of Variance↗

PubMed1990

Does moclobemide stimulate melatonin synthesis as the other selective MAO-A inhibitors do?

It has been reported that selective MAO-A inhibitors, clorgyline and brofaromine, but not the MAO-B inhibitors, deprenyl and pargyline, stimulated rat pineal melatonin synthesis in humans and animals. Recent studies, however, found no effect of moclobemide, a selective MAO-A inhibitor, on human plasma melatonin levels. Present study found that in vitro moclobemide produced very weak stimulation of rat pineal NAT activity. However, in vivo moclobemide induced a significant increase of rat pineal NAS and melatonin content, and a dramatic decrease of 5-HIAA content (HPLC-fluorimetric procedure). Moclobemide's effect on melatonin and related indoles could be detected as early as 30 min after the injection and lasted, at least, for 2 h. The possible reasons for discrepancies between human and animal data are discussed.

Acetyltransferases↗

PubMed1990

The effect of isatin (tribulin) on metabolism of indoles in the rat brain and pineal: in vitro and in vivo studies.

Isatin (Tribulin) produced a dose-dependent inhibition of both MAO A and MAO B in broken cell preparations from rat brain and pineal. However, isatin administered in vivo (80-160 mg/kg) to the intact animal significantly increased brain, but not pineal, serotonin and did not affect 5HIAA or other indoles in either brain or pineal. Further, in vivo administration did not produce detectable MAO inhibition in either tissue. In pineal organ culture, addition of isatin up to 1mM had no influence on the concentrations of pineal indoles or the activities of monoamine oxidase or serotonin N-acetyltransferase. However, the diazepam augmentation of beta adrenergic induction of serotonin N-acetyltransferase activity was blocked by isatin. The results of these studies call into question the proposed role of isatin as an endogenous monoamine oxidase inhibitor but support a possible role as a benzodiazepine receptor blocker.

Animals↗

PubMed1990

Effect of cocaine on rat pineal melatonin synthesis in vivo and in vitro.

Moderate concentrations (10 microM) of cocaine increased melatonin content and N-acetylserotonin and serotonin-N-acetyltransferase activity in rat pineal glands freshly placed in organ culture. Pineals cultured for 48 hours or taken from ganglionectomized animals did not respond to cocaine. Both procedures markedly reduced pineal noradrenalin (NA). Cocaine (5, 10, 20 mg/kg) given to adult intact rats stimulated pineal melatonin synthesis but only in animals exposed to constant light for 24 hours. Pineal denervation and/or adrenal demedullation neither completely eliminated NA from blood nor prevented cocaine-induced stimulation of melatonin synthesis in these light-primed animals.

Animals↗

PubMed1989

GM1 ganglioside treatment promotes recovery of striatal dopamine concentrations in the mouse model of MPTP-induced parkinsonism.

GM1 ganglioside (GM1) has in the past been reported to promote regenerative sprouting and functional recovery in both central and peripheral nervous systems. The present experiments were performed in order to investigate whether GM1 might have any therapeutic effect on young mice who had been exposed to the Parkinson-producing neurotoxin MPTP. GM1 caused moderate to dramatic increases in striatal dopamine levels, depending upon duration of exposure to GM1, in animals previously exposed to MPTP. Furthermore, the effects of GM1 on enhancing striatal dopamine levels were apparent when GM1 administration was delayed until 3 days after the last MPTP injection was given and these effects were not reversed when GM1 was withdrawn. Tyrosine hydroxylase (TH) immunohistochemistry of the striatum demonstrated increased numbers of TH-positive fibers and TH-positive terminal fields in GM1-treated animals as compared to animals that received only MPTP. TH immunohistochemistry of the substantia nigra revealed little or no loss of parts compacta neurons in the MPTP-treated mice. On the basis of these observations, GM1 appears to increase the dopamine content of the striatum by promoting or stimulating regenerative sprouting of dopaminergic terminals and perhaps collateral sprouting from remaining intact fibers in the MPTP model of Parkinsonism in the young mouse. We suggest that GM1 ganglioside may hold some promise as a potential adjunct in the treatment of Parkinson's Disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1989

Peptide T does not affect induction of pineal N-acetyltransferase by vasoactive intestinal peptide.

It has been suggested that the HIV virus binds to VIP recognition sites which can be blocked by the octapeptide, peptide T. Stimulation of VIP receptors on pinealocytes activates adenylate cyclase and increases the activity of the enzyme serotonin N-acetyltransferase (NAT). We examined whether peptide T or D-Ala peptide T amide affected this induction. We found no evidence for peptide T interference with NAT induction and conclude that if peptide T inhibits attachment of HIV virus to VIP receptors, it does so at regions other than that occupied by VIP in stimulating adenylate cyclase and NAT.

Acetyltransferases↗

PubMed1989

Effects of steroids on serotonin-N-acetyltransferase activity of pineals in organ culture.

Treatment of neonatal, but not adult, rats with glucocorticoids decreases the rise in pineal serotonin N-acetyltransferase activity upon stimulation with beta agonists. Pineals in organ culture and exposed to steroids also show a dose-dependent decrement in response to beta agonists which increases with steroid exposure time. Pineals from neonatal and adult animals are equally sensitive. The effects of steroids on pineals in organ culture appear to be reversible, and the order of potency of different steroids differs from that observed when steroids are administered in vivo. Both in vitro and in vivo steroids appear to act at a site after cyclic AMP generation. Hydroxyindole-O-methyltransferase activity in the adult pineal does not appear affected by steroid exposure.

Acetyltransferases↗

PubMed1988

Platelet size, number, and serotonin content in blood of autistic, childhood schizophrenic, and normal children.

Platelet volumes were measured in 19 autistic, 26 normal, and 6 schizophrenic children with similar blood serotonin concentrations. The groups did not significantly differ in platelet volumes, nor did platelet volumes and blood serotonin concentrations correlate. These results do not support the hypothesis that the hyperserotoninemia in some autistics reflects increased platelet volume.

Autistic Disorder↗

PubMed1988

Deficits in operant behaviour in monkeys treated with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Six adult Macaca fascicularis monkeys were trained to perform an instrumentally conditioned, visually-guided forearm reaching task for fruit juice reinforcement. Once animals were overtrained on this task, they were given intravenous injections of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (0.15 to 0.33 mg/kg). Animals were tested daily for performance in the previously learned behavioural task and were assessed daily for abnormalities in motor functioning. Monkeys developed deficits in operant task performance characterized by termination of responses after an initial series of responses and long pauses between responses. Once an animal stopped responding to the task, responses could often be reinitiated if the experimenter guided the monkey through the task. This type of performance deficit was seen both before and without the appearance of distinct parkinsonian motor signs. Animals which developed motor signs had extensive ventral mesencephalic cell loss while an animal with performance deficits but without motor signs had cell loss restricted to the ventral substantia nigra pars compacta. The results demonstrate that operant performance deficits can be observed in MPTP-treated monkeys independent of the appearance of motor deficits.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗