scispace - formally typeset
Search or ask a question

Showing papers on "Serotonin published in 1979"


Journal Article
TL;DR: It is proposed that [3H]5-HT and[3H]-spiroperidol label distinct populations of serotonin receptors in rat brain, designated 5-HT1 and 5- HT2 receptors, respectively.
Abstract: [3H]5-Hydroxytryptamine (5-HT), [3H]lysergic acid diethylamide (LSD) and [3H]spiroperidol bind to membranes from the rat frontal cerebral cortex in a manner indicating a selective interaction with serotonin receptors. Differential drug potencies in competing for [3H]5-HT and [3H]spiroperidol binding sites suggest that these two [3H]ligands respectively label two distinct populations of receptors, while [3H]LSD labels both the [3H]5-HT and [3H]spiroperidol sites. After incubation of brain membranes with 30 nM spiroperidol, drug specificity of the residual [3H]LSD binding resembles that of receptors labeled by [3H]5-HT. Conversely, drug effects on [3H]LSD binding in the presence of 300 nM 5-HT resemble effects with [3H]spiroperidol. We propose that [3H]5-HT and [3H]-spiroperidol label distinct populations of serotonin receptors in rat brain, designated 5-HT1 and 5-HT2 receptors, respectively. [3H]LSD appears to bind to both receptors to a similar extent.

1,353 citations




Journal ArticleDOI
TL;DR: Binding levels of tritium-LSD, presumably associated with postsynaptic 5HT receptors, were reduced 40% to 50% in samples from schizophrenics in three independent studies, whereas no other consistent alteration was observed in levels of binding associated with other receptors or in the activity of GAD.
Abstract: • Frontal cerebral cortex brain samples from schizophrenics and controls have been assayed for binding associated with muscarinic cholinergic, serotonin (5HT), γ-aminobutyric acid (GABA), and β-adrenergic receptors as well as for the activity of the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD). Binding levels of tritium-LSD, presumably associated with postsynaptic 5HT receptors, were reduced 40% to 50% in samples from schizophrenics in three independent studies, whereas no other consistent alteration was observed in levels of binding associated with other receptors or in the activity of GAD. This change in receptor binding levels does not seem to be attributable to postmortem changes, to influences of drugs received by the patients, or to demographic features of the patient populations.

256 citations


Journal ArticleDOI
TL;DR: While naloxone did not antagonize the effects of the dorsal raphe stimulation towards locus coeruleus activity, these effects were absent in rats pretreated with a serotonin synthesis inhibitor, PCPA or with 5,7‐DHT which destroys serotonin‐containing terminals, and were reduced by the serotonin antagonist methysergide.
Abstract: The connexions between the dorsal raphe nucleus and the nucleus locus coeruleus were studied in urethane anaesthetized rats. 1. Cells in the locus coeruleus gave an excitatory response to a noxious stimulus, e.g. leg pinch. 2. This excitatory response was blocked by either a parenteral or an ionophoretic injection of morphine and recovered after an injection of naloxone. 3. Electrical stimulation in the region of the dorsal raphe blocked excitatory locus coeruleus responses to noxious stimuli. 4. While naloxone did not antagonize the effects of the dorsal raphe stimulation towards locus coeruleus activity, these effects were absent in rats pretreated with a serotonin synthesis inhibitor, PCPA or with 5,7-DHT which destroys serotonin-containing terminals, and were reduced by the serotonin antagonist methysergide. 5. A serotonin-containing inhibitory pathway between the dorsal raphe and the locus coeruleus is proposed to account for these results.

245 citations


Journal ArticleDOI
TL;DR: In schizophrenic brains dopamine, noradrenaline and serotonin were significantly increased in some areas of corpus striatum, but there were no significant changes in enzyme activity or monoamine metabolite concentrations in any of the brain areas examined.
Abstract: Dopamine and its metabolites homovanillic acid and dihydroxyphenylacetic acid, noradrenaline, serotonin and its metabolite 5-hydroxyindoleacetic acid, and tryptophan and its metabolite kynurenine have been assayed in 9 schizophrenic and 10 control brains, together with the monoamine-related enzymes tyrosine hydroxylase monoamine oxidase, dopamine-beta-hydroxylase, and catechol-o-methyl-transferase. In schizophrenic brains dopamine, noradrenaline and serotonin were significantly increased in some areas of corpus striatum, but there were no significant changes in enzyme activity or monoamine metabolite concentrations in any of the brain areas examined. The findings are not consistent with theories that serotonin or noradrenaline stores are grossly depleted or noradrenaline neurones have degenerated, or that monoamine oxidase activity is abnormal, in schizophrenia, and provide no direct support for the hypothesis that dopamine neurones are overactive.

206 citations


Journal ArticleDOI
TL;DR: The data suggest that the decrease of food intake induced by metachlorophenylpiperazine depends on its ability to act as a serotonin agonist in the brain, which could prove an important tool for studies aimed at elucidating the functional role of serotonin in the central nervous system.
Abstract: Meta-chlorophenylpiperazine inhibited serotonin and noradrenaline uptake by synaptosomes to the same extent with IC50 of 1.3×10−6 M and 5.8×10−6 M respectively. Dopamine uptake was lesss affected by meta-chlorophenylpiperazine (IC50 of 2.2×10−5 M). Unlike d-amphetamine and d-fenfluramine, the drug did not significantly increase monoamine release in synaptosomal preparations. On the other hand, metachlorophenylpiperazine showed an IC50 of 620 nM in displacing 3H-5HT binding to brain membranes. Meta-chlorophenylpiperazine produced a dose-dependent reduction of food intake and this effect was prevented by a pretreatment with methergoline, a serotonin antagonist. The effect of metachlorophenylpiperazine was not modified by an intraventricular injection of 6-hydroxydopamine, electrolytic lesions of nucleus medianus raphe or ventral noradrenergic bundle, nor by a pretreatment with penfluridol, propranolol or phentolamine. The data suggest that the decrease of food intake induced by metachlorophenylpiperazine depends on its ability to act as a serotonin agonist in the brain. The specificity of the effects on serotonin suggests that this compound could prove an important tool for studies aimed at elucidating the functional role of serotonin in the central nervous system.

206 citations


Journal ArticleDOI
05 Oct 1979-Science
TL;DR: Evidence is provided for the existence of a serotonin-containing pathway seemingly analogous to the neuronal projection that terminates on small parenchymal blood vessels from noradrenergic neurons of the locus coeruleus.
Abstract: Electrolytic lesions of the nucleus raphe dorsalis and medianus reduce the concentration of serotonin (5-hydroxytryptamine) within rat brain intraparenchymal blood vessels. The concentration of serotonin within these vessels increases or decreases after the administration of drugs that modify the biosynthesis and degradation of serotonin or destroy nerve terminals by an uptake-dependent mechanism. These studies provide evidence for the existence of a serotonin-containing pathway seemingly analogous to the neuronal projection that terminates on small parenchymal blood vessels from noradrenergic neurons of the locus coeruleus.

205 citations


Journal ArticleDOI
TL;DR: Results seem to make it worthwhile to test a combination of haloperidol and a serotonin antagonist in schizophrenic patients to see whether the ratio of the therapeutic effect to the extrapyramidal side effects can be improved.

173 citations


Journal ArticleDOI
TL;DR: Reduced accumulation of CSF HVA and 5-HIAA may represent a primary decrease in brain turnover of dopamine and serotonin or a long-term adaptation to overactivity in these systems, perhaps as a result of changes in receptor sensitivity.
Abstract: Central nervous system metabolism in children with the syndrome of Gilles de la Tourette (TS) and contrasting pediatric patients was assessed by measuring the cerebrospinal fluid (CSF) metabolites of dopamine (homovanillic acid, HVA) and serotonin (5-hydroxyindoleacetic acid, 5-HIAA) with and without the administration of probenecid. Reduced accumulation of CSF HVA and 5-HIAA was found in TS. This may represent a primary decrease in brain turnover of dopamine and serotonin or a long-term adaptation to overactivity in these systems, perhaps as a result of changes in receptor sensitivity. In the CSF of a child with profound TS, an elevated level of the major metabolite of norepine.

144 citations


Journal ArticleDOI
TL;DR: It is postulate that fluoxetine, via the increase in 5-HT activity resulting from5-HT uptake blockade, inhibited both the nigro-striatal and tubero-infundibular dopaminergic neurons in man.
Abstract: Fluoxetine (Lilly 110140) is a potent, specific serotonin (5-HT) uptake blocker which is being tested in man for antidepressant activity. One of 9 depressed patients receiving this drug developed a dystonic reaction, parkinsonian rigidity, and increased serum prolactin levels, all signs of decreased dopaminergic activity. Homovanillic acid levels also decreased in the cerebrospinal fluid of this subject. We postulate that fluoxetine, via the increase in 5-HT activity resulting from 5-HT uptake blockade, inhibited both the nigro-striatal and tubero-infundibular dopaminergic neurons. These results provide additional evidence for a linkage between serotonergic and dopaminergic neurons in man.

Journal ArticleDOI
TL;DR: The data support the hypothesis that the modulatory action of serotonin at buccal muscle is mediated by CAMP, and indicate that the ARC contains a serotonin-sensitive adenylate cyclase.
Abstract: SUMMARY AND CONCLUSIONS 1. Experiments were performed to test the hypothesis that cyclic adenosine mono- phosphate (CAMP) may mediate the effects of serotonin and the metacerebral cell (MCC) on contractility of the accessory radula closer muscle (ARC) of Aplysia. 2. A cell-free homogenate of the ARC muscle showed a dose-related increase in the rate of accumulation of CAMP in the presence of serotonin. Serotonin did not reduce phos- phodiesterase activity in the muscle homog- enate. These results, therefore, indicate that the ARC contains a serotonin-sensitive adenylate cyclase. 3. The intact ARC muscle showed a dose- related increase in the synthesis (accumula- tion of radioactive precursor) and total levels of CAMP in the presence of serotonin. 4. Firing of a single MCC cell (mean, 297 spikes) produced a statistically significant increase of the synthesis of CAMP. The mean synthesis was 3.5 times higher in experimen- tal compared to paired control muscles from the same animal. This represents an 8% in- crease per MCC spike. 5. Two eighth position analogs of CAMP (8-BT CAMP and 8-PCPT CAMP) enhanced ARC muscle contractions elicited by fixed bursts of motor neuron spikes. The potentia- tion occurred in spite of the fact that the CAMP analogs reduced the size of the EJPs in the muscle. 6. The effect of the MCC in enhancing contractions of ARC muscle was enhanced in magnitude and duration by the phospho- diesterase inhibitor RO 20- 1724. 7. The data support the hypothesis that the modulatory action of serotonin at buccal muscle is mediated by CAMP.

Journal ArticleDOI
TL;DR: The results indicate that the cataleptic effect of neuroleptics depends on the balance between the dopaminergic and serotonergic systems, and that the Serotonergic system exerts an inhibitory influence on the dopaminationergic system.
Abstract: Pretreatment with quipazine, a serotonin agonist, and clomipramine, a selective serotonin neuronal uptake blocker, was found to potentiate the cataleptic effect of haloperidol in a dose-dependent manner in rats. Pretreatment with methysergide, a serotonin antagonist, reduced the cataleptic effect of haloperidol. The results indicate that the cataleptic effect of neuroleptics depends on the balance between the dopaminergic and serotonergic systems, and that the serotonergic system exerts an inhibitory influence on the dopaminergic system.

Journal ArticleDOI
TL;DR: This selective reaction, which involved approximately 1000 neurons on each side of the third ventricle, was unaltered by concomitant administration of 10 (-3) M non-radioactive norepinephrine, and was absent after intraventricular injection of 10(-5) or 10(-4) M tritiated nore Alpinephrine.

Journal ArticleDOI
TL;DR: The effects of chronic administration of clorgyline and pargyline on rat brain monoamine metabolism have been examined and dopamine appears to be dcaminated in vivo principally by MAO type A.
Abstract: The effects of chronic administration of clorgyline and pargyline on rat brain monoamine metabolism have been examined. The inhibitory selectivity of these drugs towards serotonin deamina-tion (MAO type A) and phenylethylamine deamination (MAO type B) can be maintained over a 21-day period by proper selection of low doses of these drugs (0.5-1.0 mg/kg/24h). The results are consistent with MAO type A catalyzing the deamination of serotonin and norepinephrine and with MAO type B having little effect on these monoamines. Dopamine appears to be dcaminated in vivo principally by MAO type A. Clorgyline administration during a 3-week period was accompanied by persistent elevations in brain norepinephrine concentrations; serotonin levels were also increased during the first 2 weeks, but returned towards control levels by the third week of treatment. Low doses of pargyline did not increase brain monoamine concentrations, but treatment with higher doses for 3 weeks led to elevations in brain norepinephrine and 5-hydroxytryptamine; at this time significant MAO-A inhibition had developed. The changes in monoamine metabolism seen at the end of the chronic clorgyline regimen are not due to alterations in tryptophan hydroxylase activity. At this time tyrosine hydroxylase activity was also unaffected.

Journal ArticleDOI
TL;DR: Brain serotonin turnover varies significantly only in those strains which react to isolation with a constant degree of aggressiveness and there appears to exist an inverse correlation between these two parameters.
Abstract: In the framework of aggressive behavior a great amount of studies deal with altered brain monoamine levels or turnover. The involvement of brain serotonergic mechanisms in aggression has been demonstrated in the majority of the studies. In the present work, the biochemical and behavioral changes induced by prolonged socioenvironmental isolation in seven strains of mice were studied. Brain serotonin turnover varies significantly only in those strains which react to isolation with a constant degree of aggressiveness and there appears to exist an inverse correlation between these two parameters. Nevertheless a certain degree of aggression may develop even in the absence of alterations of brain serotonin turnover. Still the intensity of serotonin turnover decrease seems to represent a good indicator of the magnitude of the aggressive reaction.

Journal ArticleDOI
TL;DR: Results are in good agreement with the relative potencies of the tricyclic antidepressants for blocking the uptake of noradrenaline and serotonin into central and peripheral neurons.

Journal ArticleDOI
TL;DR: Data indicate that (--)-cocaine and several of its derivatives inhibit 5-HT stimulation of both adrenergic and cholinergic autonomic neurones through competition with the agonist at serotonin receptor sties.

Journal ArticleDOI
TL;DR: Tryptophan and competing neutral amino acid levels were found to be diminished in the plasma of patients with multiple sclerosis and degenerative diseases, the greatest decrease being of tryptophan.
Abstract: Tryptophan and competing neutral amino acid levels were found to be diminished in the plasma of patients with multiple sclerosis and degenerative diseases, the greatest decrease being of tryptophan. Cerebrospinal fluid tryptophan was decreased in multiple sclerosis and motor neurone disease, while leucine and valine were increased. These changes might lead to decreased synthesis of brain serotonin and brain proteins. The ratio between neutral amino acids and tryptophan might be used as an ancillary test in the screening of degenerative diseases.

Journal ArticleDOI
TL;DR: It is indicated that TR has a double effect on the central 5-HT system: at low doses it acts as a5-HT antagonist, whereas at higher ones-as a 5- HT agonist, and the latter effect may be connected with formation of a metabolite, CPP, or a compound chemically related to CPP.
Abstract: We examined the effect of trazodone (TR), a non-tricyclic antidepressant drug with an unknown mechanism of action, as well as its supposed metabolitesβ-(3-oxo-s-triazolo-[4, 3 a]-pyridin-2-yl-propionic acid (OTPA) and 1-(m-chlorophenyl)-piperazine (CPP) on the serotonin (5-HT) system in a model of the hind limb flexor reflex of the spinal rat.

Journal ArticleDOI
Rex Y. Wang1, C. de Montigny1, B.I. Gold1, R. H. Roth1, George K. Aghajanian1 
TL;DR: In contrast to the marked supersensitivity seen after 5,7-DHT induced denervation, chronic administration of parachlorophenylalanine, a 5- HT synthesis inhibitor, failed to induce 5-HT supersensitivity.

Journal ArticleDOI
TL;DR: The results indicate that NCB-20 cells possess at least two species of serotonin receptors, which independently regulate cellular functions, and activation of adenylate cyclase does not directly affect membrane potential or acetylcholine release, and serotonin-dependent cell depolarization does not affect cyclic AMP or cyclic GMP synthesis in the cell lines tested.
Abstract: Serotonin activates adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] of NCB-20 neuroblastoma--brain hybrid cells with an activation constant of 530 nM, but has little or no effect on cellular cyclic AMP or cyclic GMP content of NIE-115 neuroblastoma or NG108-15 hybrid cells. In homogenates of NCB-20 hybrid cells, lysergic acid diethylamide stimulates adenylate cyclase activity (Kact = 12 nM) and partially inhibits (Ki = 10 nM) the stimulation of adenylate cyclase activity by serotonin. No desensitization was detected of serotonin receptors coupled to adenylate cyclase. Serotonin also depolarizes NCB-20, NG108-15, and NIE-115 cells and increases acetylcholine release. Serotonin receptors mediating depolarizing responses desensitize rapidly and reversibly, and the depolarizing effects of serotonin are neither mimicked nor inhibited by lysergic acid diethylamide. These results indicate that (i) NCB-20 cells possess at least two species of serotonin receptors, which independently regulate cellular functions, (ii) activation of adenylate cyclase does not directly affect membrane potential or acetylcholine release, and (iii) serotonin-dependent cell depolarization does not affect cyclic AMP or cyclic GMP synthesis in the cell lines tested.

Journal ArticleDOI
TL;DR: A model of the pathogenesis of affective spectrum disorders and their treatment and prevention with lithium is developed, based on studies of baseline and drug-induced bilateral asymmetry in tryptophan and serotonin levels in rat brain mesostriatal and mesolimbic systems.
Abstract: The purpose of this communication is to develop a model of the pathogenesis of affective spectrum disorders and their treatment and prevention with lithium; the model is based on (1) studies of baseline and drug-induced bilateral asymmetry in tryptophan and serotonin levels in rat brain mesostriatal and mesolimbic systems, (2) singlecell quantitative histochemical determinations of serotonin content in lateral median and dorsal raphe nuclei, (3) the responses of brain tryptophan hydroxylase activity to psychotropic agents, (4) in vitro studies of the kinetic properties of tryptophan hydroxylase, and (5) evidence of lateral affective specialization in human brain. The disorders are construed as diseases of regulation involving an abnormal form of brain tryptophan hydroxylase with hyperbolic substrate kinetics, possibly resulting from a hereditary defect in enzyme cooperativity or calcium metabolism or the influence of yet unidentified ligands. The abnormal enzyme kinetics would serve to amplify the functional impact of existing bilateral asymmetries

Journal ArticleDOI
TL;DR: It is reported that 1 min exposure to light 5.5 h after evcning onset of darkness causes a rapid decrease of serotonin N-acetyl transferase activity and melatonin conlent in rat pineal with a halving time less than 5 min.
Abstract: THE ACTIVITY of serotonin N-acetyltransferase (acetyl CoA: arylamine N-acetyltransferase, EC 2.3.1.5), the first specific enzyme in the branch pathway for melatonin synthesis in the rat pineal gland (WEISSBACH et al., 1960), as well as the concentration of melatonin itself (LYNCH, 1971: OZAKI et a/., 1976), exhibit a marked diurnal rhythm with night values much higher than daytime ones (KLEIN & WELLER, 1970). The rhythm is generated by sympathetic nerve terminals innervating the pineal gland, presumably by diurnal release of the neurotransmitter noradrenaline (BROWNSTEIN & AXELROD, 1974) and is abolished either by exposing rats to constant light (KLEIN & WELLER, 1970) or by denervation of the gland through bilateral superior cervical ganglionectomy or by decentralisation of the ganglia (KLEIN et a!.; 1971). Exposure of rats to light at night causes a precipitous decline in pineal N-acetyltransferase activity (KLFIN & WELLER. 1972: DEGUCHI & AXELROD, 197%) and melatonin content (ILLNEROVA et al., 1978). The drop was observed in rats exposed to light for the whole time interval before killing. The enzyme activity (KLEIN & WELLER, 1972) as well as melatonin concentration (ILLNEROVA et a/., 1978) reached their lowest level in l S 1 5 m i n . The present study was undertaken to find out, whcther even a very brief exposure to light at night-time, such as for 1 min, after which rats would continue to be in darkness, could trigger the decrease in N-acetyltransferase activity and melatonin content to low levels. We now report that 1 min cxposure to light 5.5 h after evcning onset of darkness causes a rapid decrease of serotonin N-acetyl transferase activity and melatonin conlent in rat pineal with a halving time less than 5 min. Moreover neither enzyme activity nor melatonin concentration increase again to high night lcvels within 5 h in darkness following 1 min exposure to light.

Journal ArticleDOI
TL;DR: These experiments provide convincing evidence that the soma and processes of a single neuron can contain serotonin and immunoreactivity with another putative peptide transmitter Substance P in a single permanent preparation suitable for study with light and electron microscopy.
Abstract: A novel approach is presented for combining immunocytochemistry and autoradiography after in vivo injections of monoclonal antibody to Substance P and 3H-serotonin. These experiments provide convincing evidence that the soma and processes of a single neuron can contain serotonin and immunoreactivity with another putative peptide transmitter Substance P in a single permanent preparation suitable for study with light and electron microscopy. The serotonin-Substance P cells have uptake systems for low molarity 3H-serotonin that are not affected by reserpine treatment. They are sensitive to serotonin uptake inhibitors and monoamine oxidase inhibitors and the cells are destroyed by 5,6-dihydroxytryptamine. They contain endogenous stores of serotonin detectable by the Flack-Hillarp technique and microspectrofluorimetry and immunofluorescence by antibody to serotonin. Their Substance P content is identified by specific binding with monoclonal antibody, and by animal antisera against Substance P.

Journal ArticleDOI
21 Sep 1979-Science
TL;DR: Long-term amphetamine administration to cats produced large decreases in serotonin and its major metabolite, 5-hydroxyindoleacetic acid, in all brain regions examined and produced several behaviors that are dependent on depressed central serotonergic neurotransmission and which normally are elicited exclusively by hallucinogenic drugs.
Abstract: Long-term amphetamine administration to cats (a mean of 8.75 milligrams per kilogram twice daily for 10 days) produced large decreases (40 to 67 percent in serotonin and its major metabolite, 5-hydroxyindoleacetic acid, in all brain regions examined. This treatment also produced several behaviors that are dependent on depressed central serotonergic neurotransmission, and which normally are elicited exclusively by hallucinogenic drugs. Short-term amphetamine administration (15 mg/kg) did not produce these behaviors and resulted in small decreases in brain serotonin and no change in 5-hydroxyindoleacetic acid. These data are discussed in the context of monoamine theories of schizophrenia.

Journal ArticleDOI
TL;DR: The present study evaluated the it1 uiuo effect of selective M A 0 A and B inhibitors (clorgyline and pargyline, respectively) on the metabolism of biogenic amines in man using collection and assay procedures which have been previously described.
Abstract: IN 1968, JOHNSTON described-two forms of monoamine oxidase (MAO) on the basis of a bimodal pattern of inhibition of tyramine deamination found with clorgyline (JOHNSTON, 1968). Later studies revealed that M A 0 type A preferentially deaminates 5-hydroxytryptamine (5-HT) and norepinephrine (NE) and is more susceptible to inhibition by clorgyline; in contrast M A 0 type B more readily deaminates ,!I-phenylethylamine and is preferentially inhibited by deprenyl (KNOLL & MAGYAR, 1972) and pargyline (SQUIRES, 1972). Dopamine and tyramine are substrates for both forms of the enzyme (YANG & NEFF, 1974). Many mammalian tissues contain both these forms of the enzyme: but the apparent proportion of the two forms vary widely between various organs in an individual species as well as between different species, making extrapolation to man difficult (SQul~ts, 1972; TIPTON ef a!., 1976). The present study was undertaken to evaluate the it1 uiuo effect of selective M A 0 A and B inhibitors (clorgyline and pargyline, respectively) on the metabolism of biogenic amines in man. Cerebrospinal fluid samples were obtained from seven hospitalized depressed patients at the end of a 3-week period off all drugs. Six patients were subsequently treated with clorgyline (May & Baker, Ltd., Essex, England), 2@30mg/day, and were resampled in the fourth week of treatment. Five were treated with pargyline (Abbott Pharmaceutical Division, Chicago, IL) (75-100 mglday) and also were resampled in the fourth treatment week. The four patients in this group who received both clorgyline and pargyline (as part of a randomized, cross-over trial described in detail elsewhere) (MURPHY et a/., in press) had a 3-week placebo period between the trials with the two drugs. The cerebrospinal fluid samples werc obtaincd at 8 a.m. after 8 h of bed rest for the determination of homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxy-4-hydroxyphenylglycol (MHPG), 3-methoxy-4-hydroxy-~-mandelic acid (VMA), and 5-hydroxyindoleacetic acid (5-HIAA) following collection and assay procedures which have been previously described (ASHCROFT e t a / . , 1966; GORDON et a/., 1974, 1976; WATSON et a/., 1974). The monoamine metabolites measured before and after clorgyline and pargyline treatment are presented in Table 1. HVA, the major acidic metabolite of dopamine, was significantly decreased during clorgyline (P < 0.02, paired t-test). as well as pargyline ( P i 0.01) treatment, although pargyline caused a significantly greater reduction than clorgyline ( P < 0.05) (Fig. I ) . MHPG, the main metabolite of norepinephrine was markedly reduced ( P < 0.01) to an equal extent by both drugs. Neither VMA, a minor metabolite of norepinephrine, nor DOPAC, a minor metabolite of dopamine, was significantly affected by either drug. 5-HIAA, the main metabolite of serotonin was significantly reduced by both clorgyline ( P < 0.02) and pargyline ( P i 0.05) as measured by the gas chromatography-mass spectroscopy (gc-ms) method. The fluorimetricallymeasured values for 5-HIAA were not comparable. They were significantly higher than the gc-ms values for patients receiving clorgyline (P < 0.02) as well as pargyline ( P < 0.05). and no significant reductions from baseline were observed during treatment with either drug using thc values from the fluoronietric assay. There are numerous reports in the literature showing both A and B forms of M A 0 in brain of various species including man (JOHNSTOX, 1968; HALL et a!., 1969). Human brain has been shown to contain predominantly MAO-B activity (GLOVER et a/., 1977), and preliminary data from our laboratory indicates that human cortex contains approx 80% B type enzyme and 20% A type. Since dopamine is a substrate for both forms of the enzyme, the greater reduction in HVA, the major metabolite of dopamine, by the MAO-B inhibitor pargyline, was expected.

Journal ArticleDOI
TL;DR: Findings support a transmitter role of GABA in NDR and may be interpreted related to a decreased activity of serotonin.

Journal ArticleDOI
TL;DR: The role played by brain serotonin (5-HT) neurotransmission in mediating the PRL-releasing effect of enkephalins was investigated in the rat and Metergoline significantly reduced the increase in plasma PRL due to EKNH2.
Abstract: The role played by brain serotonin (5-HT) neurotransmission in mediating the PRL-releasing effect of enkephalins was investigated in the rat. Both MetG-enkephalin (Metenk) and (D-Met2, Pro5)-enkephalinamide (EKNH2), an analog with long lasting analgesic activity, were used in freely moving rats bearing a cannula chronically implanted into the jugular vein. Met-enk injected intracerebroventricularly (IVT; 200 and 400 μg/rat) induced a marked and dose-related increase in plasma PRL; EKNH2 (0.2 mg/kg, iv) induced a rise in plasma PRL similar to that evoked by Met-enk (400μg/rat). Metergoline (1 mg/kg, iv), a 5-HT receptor blocker, significantly reduced the PRL-releasing effect of Met-enk (200 μg/rat); these results were duplicated by using another 5-HT receptor blocker, i.e. methysergide (2.5 mg/kg, iv). Metergoline and methysergide also significantly reduced the increase in plasma PRL due to EKNH2. 5,6-Dihydroxytryptamine (50 μg, IVT), a neurotoxic drug which destroys 5-HT nerve terminals, almost completely...

Journal ArticleDOI
TL;DR: The data suggest that the long-term effects of fenfluramine on brain 5-HT neurons can not be explained by a single mechanism such as an irreversible cytotoxic action, and that the reduction in enzyme activity is mediated by a mechanism different from that responsible for the decreases in the other parameters.