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Biomedical subjects

A Yuwiler

Publications and source records attributed to A Yuwiler.

At least 37 records · Page 2Linked to original sources
PubMed1988

Effect of selective monoamine oxidase inhibitors on rat pineal melatonin synthesis in vitro.

Freshly cultured pineal glands respond to the monoamine oxidase A (MAO A) inhibitor clorgyline and to high concentrations of the MAO B inhibitor, deprenyl, with an increase in serotonin N-acetyltransferase activity and N-acetylated indoles and a fall in 5-hydroxylated serotonin degradation products. Glands cultured for 48 hours before challenge respond less. Response is absent in glands cultured for 72 hours and in glands from ganglionectomized animals cultured for 48 hours before challenge. These data are consistent with the hypothesis that these MAO inhibitors stimulate melatonin synthesis by protecting norepinephrine from degradation.

Animals↗
PubMed1987

Selective loss of subpopulations of ventral mesencephalic dopaminergic neurons in the monkey following exposure to MPTP.

Tyrosine hydroxylase immunohistochemical examination of the mesencephalon of severely parkinsonian MPTP-treated macaque fascicularis monkeys revealed a marked loss of substantia nigra pars compacta (SNc) neurons in both medial and central portions of the nucleus with a relative sparing of neurons in the dorsal-most portions of the substantia nigra. These animals also sustained 20-65% loss of neurons in the substantia nigra pars lateralis area, ventral tegmental area (A-10), and the retrorubral area (A-8 cell group, and the parabrachialis pigmentosus region). These animals all had extreme striatal dopamine depletions. A monkey which received several small doses of MPTP and yet remained asymptomatic for a motor disorder (although it had demonstrable behavioral performance deficits) had only a loss of ventral SNc neurons, with no appreciable cell loss in associated ventral mesencephalic dopamine areas and no loss of striatal dopamine. These data suggest that the effects of MPTP are not as selective as originally thought and, more importantly, indicate that MPTP-induced parkinsonism in the primate may be more analogous to idiopathic Parkinson's disease, where cells other than SNc cells are affected. Furthermore, the present findings suggest that only certain mesencephalic dopamine neurons are susceptible to MPTP-induced damage. The unique characteristics of these neurons need to be elucidated.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

L-5-hydroxytryptophan attenuates positive psychotic symptoms induced by D-amphetamine.

Brain serotonin has been hypothesized to be involved in the modulation of psychotic symptoms in at least some forms of schizophrenia. We examined the effects of the serotonin precursor L-5-hydroxytryptophan (5HTP) on D-amphetamine induction of acute psychotic symptoms in schizophrenic patients. Preadministration with 5HTP significantly antagonized amphetamine-elicited elevations in thought disturbance, activation, and hallucinations.

5-Hydroxytryptophan↗
PubMed1987

Synergistic action of postsynaptic alpha-adrenergic receptor stimulation on vasoactive intestinal polypeptide-induced increases in pineal N-acetyltransferase activity.

The alpha-adrenergic agonists phenylephrine and methoxamine, at concentrations that have little effect on pineal N-acetyltransferase activity, markedly enhance stimulation of this enzyme by vasoactive intestinal polypeptide (VIP). This augmentation can be blocked by the alpha 1-adrenergic antagonists phenoxybenzamine and prazosin and, at 10 but not 1 microM, by the alpha 2-antagonist yohimbine. The time course for VIP stimulation is not altered by concomitant alpha-adrenergic stimulation. Augmented activity does not require concomitant alpha-adrenergic stimulation, but alpha-adrenergic agonists must be present for augmentation to be maintained. Phorbol 12,13-diacetate or -dibutyrate but not 4 alpha-phorbol can substitute for phenylephrine, a finding suggesting that protein kinase C is involved in the augmentation. These results are, in general, analogous to alpha-adrenergic magnification of N-acetyltransferase induction by beta-adrenergic agonists.

Acetyltransferases↗
PubMed1987

Catecholaminergic activity in idiopathic torsion dystonia.

Day and nighttime melatonin and dopamine-beta-hydroxylase activity were measured in blood from 10 Jewish and 9 non-Jewish dystonics and from 22 nondystonic family members. Groups did not significantly differ on either of these measures. These results do not support a generalized abnormality of noradrenergic release in dystonia.

Adolescent↗
PubMed1986

Effects of chronic fenfluramine on blood serotonin, cerebrospinal fluid metabolites, and behavior in monkeys.

The effects of long term (70 days) fenfluramine treatment on selected physiological and behavioral measures were examined in four adult male vervet monkeys (Cercopithecus aethiops sabaeus). Relative to pretreatment baseline values, whole blood serotonin (WBS) and cerebrospinal fluid 5-hydroxyindole acetic acid (5-HIAA) were reduced, cerebrospinal fluid homovanillic acid (HVA) was unaltered, and aggressive and locomotor behavior were increased. Both physiological and behavioral effects were reversible: all measures returned to baseline values in the 35 day post-treatment period, with WBS resuming pretreatment values more rapidly than CSF 5-HIAA. At the relatively low doses (1-4 mg/kg/day) employed in the present study fenfluramine produced behavioral effects similar to those resulting from PCPA and opposite to those following tryptophan administration. Thus the behavioral effects of long-term fenfluramine may involve reductions in serotonergic transmission.

Aggression↗
PubMed1986

Production of a Parkinson-like syndrome in the cat with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): behavior, histology, and biochemistry.

N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a potent dopaminergic neurotoxin, was administered to cats systemically for 5 to 7 days. This treatment produced a behavioral syndrome characterized by akinesia, ataxia, bradykinesia, and feeding difficulties, lasting for several weeks. During this period of severe behavioral impairment, caudate and nucleus accumbens dopamine and norepinephrine concentrations were quite depleted. Behavioral recovery ensued over the next several weeks as did some recovery of striatal catecholamines. MPTP destroyed the majority of substantia nigra pars compacta neurons while affecting a much lesser number of locus ceruleus and ventral tegmental neurons. These results demonstrated for the first time that MPTP can cause long-lasting deficits in nigrostriatal functioning in the cat and may provide a means for studying the apparently selective neurotoxic effects of MPTP as well as for understanding the pathophysiology of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Untoward effects of fenfluramine in autistic children.

Several recent studies have described the benefits of fenfluramine for the symptomatic treatment of infantile autism. No large surveys of side effects of this drug have been reported in autistic children. To evaluate the untoward effects of fenfluramine in children with autism, 12 subjects were systematically studied. Medication was administered in a double-blind, placebo-controlled cross-over study. Parents were trained in monitoring untoward effects. These observations were compiled in detailed daily notes. In addition, four cases describing unusual effects found in a sample of 170 patients treated with fenfluramine are also reported. In the initial 2 weeks of active drug listlessness, food refusal, and stomach upset were frequently seen. A different pattern of untoward effects was seen in the final 14 weeks of treatment. Irritability, agitation, and crying along with continued food refusal were noted. The subjects lost 2.1% of body weight during active drug phase, but there was a rebound weight gain during the subsequent placebo phase. A thorough understanding of fenfluramine's side effects and adverse reactions is necessary so as to differentiate them from the multiple symptoms inherent in the syndrome of autism.

Adolescent↗
PubMed1985

Dominant social status facilitates the behavioral effects of serotonergic agonists.

The effects of dominance rank on the behavioral responses to drugs that enhance central serotonergic function were examined in 45 adult male vervet monkeys living in 15 stable social groups. Each group contained 3 adult males, 3 adult females, and their immature offspring. Dominance rank was assessed by measuring success in intermale agonistic encounters. In every group one male was clearly the dominant, or alpha male, and the other two males were subordinate. Males from 5 groups received 3 doses of the serotonin reuptake inhibitor fluoxetine (0.5, 1.0 and 2.0 mg/kg/day); those from a second set of 5 groups received 3 doses of the receptor agonist quipazine (0.25, 0.50 and 1.0 mg/kg/day); those from a third set of 5 groups received the serotonin precursor tryptophan (10, 20 and 40 mg/kg/day). The 3 drug treatments produced strikingly similar behavioral effects. Each produced dose-dependent increases in approaching, grooming, resting and eating and decreases in locomoting, avoiding, being vigilant and being solitary. Dominant males were significantly more responsive behaviorally to all 3 drugs than were subordinate males: the increase or decrease in each behavioral measure was larger in dominant than in subordinate males. In combination with previous studies, these data suggest that dominant and subordinate males differ in the drug sensitivity of their serotonergic systems.

Age Factors↗
PubMed1985

Comparison of hyperactivity in adult rats induced by neonatal intraventricular 6-hydroxydopamine following pargyline or desmethylimipramine treatment.

The relative roles of norepinephrine (NE) and dopamine (DA) in sustaining neonatal hyperactivity were assessed in rats given 6-hydroxydopamine (6-OHDA) neonatally into the lateral ventricles after pargyline (P) or desmethylimipramine (DMI) pretreatment. On day 5 after birth, male and female rat pups were pretreated with P (50 mg/kg IP) or DMI (25 mg/kg IP) 30 min before receiving bilateral injections of 6-OHDA (200 micrograms/5 microliters saline containing ascorbic acid 1.0 mg/ml) into the lateral ventricles. Controls were pretreated with P or DMI and then received injections of saline containing the ascorbate. Spontaneous activity was measured in a stabilimeter at ages 30-31, 42-45, 60-63, 75-77, and 120-122 days. Activity in controls and P + 6-OHDA animals was also measured at 254 days of age. The sessions lasted 45 min, except those testing activity in the 254-day-old rats which lasted 12 h. Regional assays of catecholamines carried out when the animals were 150 days old revealed that in the P + 6-OHDA group the levels of NE were reduced in frontal cortex (7% of control levels), caudate (21%), and hippocampus (14%). The NE levels were unchanged or slightly elevated in hypothalamus, ventral midbrain, and pons. The DA levels in the P + 6-OHDA group were depleted in caudate (8%) and ventral midbrain (32%), and unchanged in hypothalamus and pons. In the DMI + 6-OHDA group the NE levels were reduced in caudate (25%) and elevated in hippocampus (188%). The DA levels were depleted in caudate (3%) and ventral midbrain (22%).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1985

Neonatal steroid treatment reduces catecholamine-induced increases in pineal serotonin N-acetyltransferase activity.

Hydrocortisone acetate given to the neonatal rat diminishes subsequent elevations in pineal serotonin N-acetyltransferase (acetyl-coenzyme A:arylamine N-acetyltransferase; EC 2.3.1.5; NAT) activity produced by administration of catecholamines to the intact animal or to pineals in organ culture. The time required for development of this decrease in sensitivity varies inversely with age at treatment. A minimal dose of 200 micrograms of hydrocortisone acetate/rat is required to elicit this decreased response to agonist. Other glucocorticoids have qualitative effects similar to hydrocortisone acetate, but cholesterol and the gonadal steroids testosterone, estradiol, and progesterone are without effect. In addition to showing a smaller rise in NAT activity on stimulation, pineals from steroid-treated neonates also synthesize less N-acetylserotonin and melatonin from tryptophan. The decrease in NAT response to stimulation after steroid treatment appears due to actions beyond cyclic AMP generation and may involve inhibition of protein synthesis.

Acetyltransferases↗
PubMed1985

Effects of 6-methoxy-2-benzoxazolinone on the pineal melatonin generating system.

6-Methoxy-2-benzoxazolinone (6-MBOA) at concentrations greater than 20 microM stimulates serotonin N-acetyltransferase (NAT) activity of rat pineal glands in 48-hr organ culture as well as of glands freshly cultured, indicating that 6-MBOA acts postsynaptically. The effects of 6-MBOA on NAT activity can be blocked by propranolol but not by prazosin, suggesting that 6-MBOA acts on the beta receptor. At the doses used 6-MBOA stimulation does not block or enhance NAT stimulation by norepinephrine, but is additive with vasoactive intestinal polypeptide which stimulates NAT activity at a site different than the beta receptor. This study demonstrates that 6-MBOA stimulates rather than inhibits melatonin biosynthesis and does not prevent stimulation of melatonin synthesis by norepinephrine. The progonadal association with eating plants containing 6-MBOA in the Montane vole may be due to over stimulation of melatonin receptor sites. Other possible explanations include an extrapineal action such as a blockade of melatonin receptors in the central nervous system, a blockade of receptors on the gonads or to a direct action of this agent on the gonads.

Acetyltransferases↗
PubMed1984

Social and environmental influences on blood serotonin concentrations in monkeys.

Dominant male adult vervet monkeys have whole-blood serotonin concentrations approximately twice those of subordinate adult males. We examined the effects of spontaneous and induced changes in social status, temporary isolation from the social group, and membership in single male groups on whole-blood serotonin concentrations. We found that in male vervet monkeys, elevated blood serotonin concentration is a state-dependent consequence of active occupation of the dominant male social position, and we believe that a reinterpretation of the significance of hyperserotonemia in humans may be warranted.

Animals↗
PubMed1984

Study of fenfluramine in outpatients with the syndrome of autism.

Fenfluramine was administered to 14 outpatient children with the syndrome of autism to determine whether previously produced decreases in blood serotonin concentrations and clinical improvements could be reinstituted. A double-blind medication-placebo crossover design was used. Each patient received fenfluramine 1.5 mg/kg daily (0.75 mg/kg twice daily) for 8 months, followed by placebo for 2 months. Blood serotonin levels promptly fell approximately 49% regardless of baseline levels. Clinical improvement returned, and on some scales gains after 8 months exceeded those noted after only 4 months of treatment. Significant correlations emerged among the amount of clinical response, initially high verbal IQs, and low blood serotonin concentrations. Compliance was excellent, and no clinically relevant side effects or weight changes occurred. It appears that fenfluramine is effective in ameliorating specific symptoms in certain autistic patients. The extent and mechanism of its action remain to be discovered.

Adolescent↗
PubMed1983

Light and agonists alter pineal N-acetyltransferase induction by vasoactive intestinal polypeptide.

Vasoactive intestinal polypeptide stimulated serotonin N-acetyltransferase activity in rat pineal glands in organ culture by a postsynaptic action that was independent of the beta-receptor. The magnitude of stimulation could be altered by environmental lighting conditions and by prior exposure to the agonist. Such up- and down-regulation, well known for catecholaminergic stimulation of this system, is compatible with a possible control of the pineal by vasoactive intestinal polypeptide as well as by catecholamines.

Acetyltransferases↗