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Biomedical subjects

A Yuwiler

Publications and source records attributed to A Yuwiler.

At least 19 recordsLinked to original sources
PubMed1997

Modulation of the inhibitory effect of phenylethylamine on spontaneous motor activity in mice by CPP-(+/-)-3-(2-carboxypiperazin-4-YL)-propyl-1-phosphonic acid.

Beta-phenyl-ethylamine (PEA) at dose of 50 mg/kg inhibits spontaneous, motor activity in mice. CPP- (+/-)-3-(2-Carboxypiperazin-4-yl)-propyl-1-phosphonic acid, a selective and competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, in doses of 0.2-10 mg/kg dose-dependently antagonizes this inhibitory effect of PEA. This effect of CPP appeared to be selective because the inhibitory action of PEA was not altered by pretreament with noncompetitive antagonists of NMDA receptors, such as dizocilpine (MK-801), phencyclidine (PCP), 1-phenylcyclohexylamine (PCA) or by antagonists of other behavioral effects of PEA such as haloperidol, baclofen and phenibut (beta-phenyl-GABA). CPP failed to antagonize the inhibitory effect of other tested drugs such as diazepam, haloperidol, baclofen and phenibut. Intracerebroventricularly administered NMDA (0.2 microM), an agonist of NMDA receptors, suppressed the antagonistic effects of CPP against PEA. This suggests that anti-PEA effect of CPP is related to NMDA receptors. Anti-PEA effect of CPP is not due to accelerated deamination of PEA in CPP-treated mice. When small doses of PEA (5 and 10 mg/kg) and CPP (0.2 and 1 mg/kg) were used, the synergism of two drugs was observed. CPP (1 mg/kg) and deprenyl (0.5 mg/kg) an inhibitor monoamine oxidase of B type (MAO-B), had additive effects on PEA-induced inhibition of locomotion. This effect was not associated with any further inhibition of activity of brain MAO-B (over the inhibition induced by deprenyl alone-by 65%) under high (80 microM) or low (4.3 microM) concentration of PEA as a substrate in the medium. Mechanism of the interaction of CPP and PEA, two drugs belonging to different groups of biologically active compounds, deserves further studies.

Animals↗
PubMed1996

Effects of nerve growth factor on splenic norepinephrine and pineal N-acetyl-transferase in neonate rats exposed to alcohol in utero: neuroimmune correlates.

Prenatal alcohol exposure (FAE) has been associated with multiple anomalies, including a selective developmental delay of sympathetic innervation in lymphoid organs. Sympathetic neurons require nerve growth factor (NGF) for their development and maintenance, and recent evidence has suggested that alcohol impairs the synthesis and/or biological activity of NGF in selected central and peripheral neurons. Thus, the present study examined the hypothesis that NGF administration to FAE rats during early postnatal development would reverse some of the peripheral sympathetic deficits. Neonate rats, FAE and the corresponding control cohorts, received daily treatments of NGF or cytochrome C (0.3 mg/kg; s.c.) for various time intervals, and were killed 24 hr or 10 days after the last treatment. The measured parameters included norepinephrine (NE) concentrations in the spleen and heart, which receive nor-adrenergic innervation from the coeliac ganglion and the superior cervical ganglion (SCG), respectively. In addition, we measured the activity of pineal N-acetyltransferase (NAT), the rate-limiting enzyme of melatonin biosynthesis, which depends on sympathetic innervation from the SCG. The data show that chronic, but not acute, NGF treatments reversed the FAE-related deficits in splenic NE concentrations as well as in pineal NAT activity in a time- and age-dependent manner. Sympathetic neurons play an important role in immune modulation. Thus, the altered splenic NE levels and pineal NAT activity may play a role in immune deficits associated with exposure to alcohol in utero.

Animals↗
PubMed1995

Distribution of fluphenazine and its metabolites in brain regions and other tissues of the rat.

Rats were given 5, 10, or 20 mg/kg oral doses of fluphenazine (FLU) dihydrochloride daily for 15 days. FLU and its sulfoxide (FL-SO), 7-hydroxy (7-OH-FLU) and N4'-oxide (FLU-NO) metabolites were assayed in plasma, liver, kidney, fat, whole brain, and brain regions by specific and sensitive radioimmunoassays (RIA). All metabolites were detected in tissues at higher levels than in plasma, and the levels increased with dose. FLU was 10- to 27-fold higher in brain regions than in plasma. Brain vs plasma levels of FLU correlated more closely than levels of its metabolites. Liver contained the highest levels of all analytes at all doses. FLU-SO was the major metabolite in brain regions (24% to 96% of FLU) and accumulated in fat 43 to 75 times more than FLU. Levels of 7-OH-FLU and FLU-NO were very low in brain (1% to 20% of FLU). FLU-SO and FLU-NO had only 1% to 3% the affinity for D1 and D2 receptors, but 7-OH-FLU had 20% the D2 and 5% the D1 affinity of FLU. The low affinity for dopamine receptors and low brain-levels of metabolites of FLU indicate that they are not likely to contribute importantly to pharmacologic responses of FLU. Also, the estimated relative "activity factor" for these compounds in the brain indicated that the contribution to neuropharmacologic activity by metabolites is less than 1% of FLU. Consequently, clinical monitoring of plasma FLU alone may be sufficient.

Animals↗
PubMed1995

Interaction between adrenergic and peptide stimulation in the rat pineal: pituitary adenylate cyclase-activating peptide.

The 27 amino acid peptide, pituitary adenylate cyclase-activating polypeptide (PACAP-27), and its 38 amino acid analogue, PACAP-38, stimulate serotonin-N-acetyltransferase (NAT) activity and N-acetylserotonin (NAS) and melatonin content of pineal glands from adult rats. Maximal stimulation of rat pineal NAT by PACAP-38 is not increased further significantly by concurrent stimulation with the two related peptides, vasoactive intestinal polypeptide (VIP) and/or peptide N-terminal histidine C-terminal isoleucine (PHI). Isoproterenol was a more potent inducer of NAT activity than any of these peptides alone or in combination. PACAP-38 also stimulates melatonin production by chicken pineal cells in culture as does VIP. Stimulation by both was not greater than after either alone. Prior stimulation of rat pineal NAT activity with VIP, PHI, or PACAP-38 reduces the magnitude of subsequent stimulation with PACAP-38 or forskolin. Concurrent stimulation of alpha-receptors or treatment with active phorbol ester augments rat pineal response to PACAP-38 stimulation just as it increases the response to VIP, PHI, and beta-receptor stimulation. Pineals from newborn rats respond to PACAP-38 with an increase in NAT activity and the increase is augmented by concomitant alpha 1-adrenergic stimulation. The putative PACAP inhibitor PACAP (6-38) and the putative VIP inhibitor (Ac-Tyr,D-Phe)-GRF 1-29 amide, in 100-1,000-fold excess, did not affect the stimulatory activity of any of the peptides. Pineal melatonin concentration parallels changes in pineal NAT activity.

Adenylyl Cyclases↗
PubMed1995

Whole blood serotonin and disruptive behaviors in juvenile obsessive-compulsive disorder.

OBJECTIVE: The study was conducted with children and adolescents with obsessive-compulsive disorder (OCD) to assess the relationship of whole blood serotonin (5-HT) content to a concurrent diagnosis of a disruptive behavior disorder (DBD) and to severity ratings of aggressive behavior. METHOD: Eighteen children and adolescents who met DSM-III-R criteria for OCD were evaluated with a structured interview, clinician rating scales, and the Child Behavior Checklist (CBCL). Blood 5-HT concentration was assayed with a fluorometric procedure. Relationships among categorical diagnoses, dimensional ratings, and blood 5-HT content were analyzed with bivariate and multivariate techniques. RESULTS: OCD subjects with a DBD (n = 6) had significantly higher scores than those without a DBD (n = 12) on the Total Problem scale, the Externalizing Problem scale, and several of the behavioral syndrome scales of the CBCL. Blood 5-HT concentrations were significantly lower in those with a DBD than in those without a DBD, and blood 5-HT concentrations had significant negative correlations with the Total score, the Externalizing score, and the Aggressive Behavior score of the CBCL. CONCLUSIONS: The results provide further evidence of a significant relationship between aggressive behavior and serotonergic functioning.

Adolescent↗
PubMed1995

Prenatal alcohol exposure and pineal response to isoproterenol, vasoactive intestinal polypeptide, and desmethylimipramine.

Pineals from neonatal rats born to alcohol-fed mothers had lower unstimulated serotonin-N-acetyltransferase activity (NAT) and responded less to isoproterenol, vasoactive intestinal polypeptide, or desmethylimipramine challenge than did pineals from pups born to normal or pair-fed mothers. Group differences disappeared after the first week of life. Reduced NAT activity is coincident with elevated glucocorticoids in these pups. In contrast to these effects of chronic in utero ethanol exposure, acute ethanol addition to normal adult pineals in organ culture enhanced ISO but not VIP stimulation of NAT activity. The results suggest that the neonatal pineal is more affected by ethanol-induced activation of the adrenocortical axis during gestation than by the direct effect of ethanol on membrane fluidity.

Animals↗
PubMed1994

Synergistic sedative effect of selective MAO-A, but not MAO-B, inhibitors and melatonin in frogs.

Total suppression of righting reflex in frogs (Rana pipiens, 25-35 mg b.w.) was observed after combined administration of melatonin (12.5 mg/kg) and selective inhibitors of MAO-A: clorgyline (2.5 mg/kg) and moclobemide (50 mg/kg) but not MAO-B: selegiline (25 mg/kg) and Ro-19-6327 (50 mg/kg). None of these drugs alone affected the righting reflex. Clorgyline and selegiline selectively inhibited brain MAO-A and MAO-B activity (by more than 90%), resp. Frogs might represent a convenient model to study the selective MAO-A and B type inhibitors since they provide the opportunity to correlate behaviour and biochemical changes induced by MAO inhibitors.

Animals↗
PubMed1994

The effect of 6-months l-deprenyl administration on pineal MAO-A and MAO-B activity and on the content of melatonin and related indoles in aged female Fisher 344N rats.

Six months of administration of the selective MAO-B inhibitor, selegiline (l-deprenyl 0.25 mg/kg, s.c.) to aged female Fisher 344N rats suppressed MAO-A as well as MAO-B activity and increased serotonin (substrate for melatonin biosynthesis) and N-acetylserotonin (immediate melatonin precursor) levels in pineal glands taken from the animals during the night. Daytime values were unchanged by the treatment. The data suggest that stimulation of pineal melatonin biosynthesis might be one of the consequences of MAO-A inhibition contributing to life span prolongation induced by chronic selegiline treatment.

Aging↗
PubMed1994

Chronopharmacological study of moclobemide effect on the rat pineal melatonin biosynthesis.

The chronopharmacological hypothesis of the mechanism of the antidepressant effect of MAO-A inhibitors predicts that clinical efficacy depends upon the time of the day at which the drugs are administered. In the present study moclobemide (10 mg/kg, s.c.) injected at the end of the light phase advanced the onset of the nighttime increase of the rat pineal melatonin biosynthesis while the same dose of drug injected at the end of the dark phase delayed the daytime decrease of melatonin biosynthesis. The results obtained suggest that the timing of MAO-A inhibitor administration should be considered in clinical practice.

Animals↗
PubMed1994

The acute effect of the bioprecursor of the selective brain MAO-A inhibitor, MDL 72392, on rat pineal melatonin biosynthesis.

The bioprecursor amino acid MDL 72394 is decarboxylated by aromatic L-amino acid decarboxylase (AADC) to liberate MDL 72392, an irreversible selective MAO-A inhibitor. Pretreatment with the AADC inhibitor carbidopa, which does not penetrate the brain-blood barrier, prevents the liberation of the MAO-A inhibitor outside the brain and results in exclusive inhibition of brain MAO-A. We found that systemic administration of MDL 72394 (0.5 mg/kg, i.p.) stimulated rat pineal melatonin biosynthesis. Carbidopa, in a dose-dependent manner, attenuated or completely prevented MDL-induced stimulation of melatonin biosynthesis in the pineal gland located outside the blood-brain-barrier.

Animals↗
PubMed1993

Commonalities in vasoactive intestinal peptide and peptide N-terminal histidine C-terminal isoleucine stimulation of N-acetyltransferase activity in the rat pineal.

Exposure of adult rat pineal glands in organ culture to the polypeptides vasoactive intestinal polypeptide (VIP), and peptide N-terminal histidine C-terminal isoleucine (PHI) increases pineal serotonin N-acetyltransferase (NAT) activity and melatonin synthesis. The following research results are taken to indicate that VIP and PHI share common components of the NAT induction system: (1) The effects of the two peptides are additive at concentrations of 10 nM VIP and 100 nM PHI but not at higher peptide concentrations. (2) Pineals from newborns also respond to PHI with a dose dependent increase in NAT activity. NAT responses are additive at the same concentrations as seen with the adult pineals. (3) Light exposure affects the sensitivity of pineals to VIP and PHI stimulation in a similar manner; pineals taken after 3 hr of light are much less sensitive to PHI or VIP than those taken after 13 hr of light. (4) Pineals exposed for 48 hr to either PHI or VIP have a reduced NAT response to either agonist, which is reversible by culture in agonist-free media. (5) Neither VIP nor PHI stimulation of NAT activity is affected by concentrations of the VIP antagonists (N-Ac-Tyr1,D-Phe2)-GRF(1-29)-NH2 (NAcTDGRF), L-8-K, VIP-Neurotensin Hybrid (VIPNET), or (4Cl-D-Phe6, Leu17)-VIP (4C1PLVIP), which affect VIP binding or function in other tissues.

Amino Acid Sequence↗
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↗