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Journal ArticleDOI

Serotonin-norepinephrine interactions: a voltammetric study on the effect of serotonin receptor stimulation followed in the N. raphe dorsalis and the Locus coeruleus of the rat.

01 Jan 1992-Journal of Neural Transmission (J Neural Transm Gen Sect)-Vol. 88, Iss: 1, pp 11-23
TL;DR: In vivo voltammetry with carbon fibre electrodes was used to study the effect of the serotoninergic (5-HT) neuronal system on the noradrenergic (NE) system in the Locus coeruleus of the rat, and ritanserin increased the 5-HIAA signal in this nucleus.
Abstract: In vivo voltammetry with carbon fibre electrodes was used to study the effect of the serotoninergic (5-HT) neuronal system on the noradrenergic (NE) system in the Locus coeruleus of the rat. The voltammetric DOPAC signal in the Locus coeruleus, used as a measure of NE neuronal activity, was increased after systemic application of the 5-HT1B agonist CGS-12066B, the 5-HT2 antagonist ritanserin, and, to a lesser extent, by ipsapirone, a 5-HT1A agonist. The findings suggest that the NE neuronal system of the Locus coeruleus is stimulated by 5-HT1A and 5-HT1B receptor activation and inhibited by 5-HT2 receptors. Likewise the 5-HT releaser and uptake inhibitor fenfluramine increased the DOPAC level in the Locus coeruleus. In contrast to the 5-HT1 agonists, which reduced 5-hydroxyindoleacetic acid (5-HIAA) in the Nucleus raphe dorsalis, ritanserin increased the 5-HIAA signal in this nucleus. This finding could help to explain the action of ritanserin as sleep-modulating substance.
Citations
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Journal ArticleDOI
01 Jun 2000-Synapse
TL;DR: 5‐HT2C receptors exert a tonic, suppressive influence on the activity of mesocortical — as well as mesolimbic and nigrostriatal — dopaminergic pathways, likely via indirect actions expressed at the level of their cell bodies.
Abstract: The present study evaluated, via a combined electrophysiological and dialysis approach, the potential influence of serotonin (5-HT)2C as compared to 5-HT2A and 5-HT2B receptors on dopaminergic, adrenergic, and serotonergic transmission in frontal cortex (FCX). Whereas the selective 5-HT2A antagonist MDL100,907 failed to modify extracellular levels of dopamine (DA), noradrenaline (NA) or 5-HT simultaneously quantified in single dialysate samples of freely-moving rats, the 5-HT2B/5-HT2C antagonist SB206,553 dose-dependently increased levels of DA and NA without affecting those of 5-HT. This action was attributable to 5-HT2C receptor blockade inasmuch as the selective 5-HT2C antagonist SB242,084 likewise increased FCX levels of DA and NA, whereas the selective 5-HT2B antagonist SB204,741 was ineffective. Further, the preferential 5-HT2C receptor agonist Ro60-0175 dose-dependently depressed FCX levels of DA. The suppressive influence of 5-HT2C receptors on DA release was also expressed on mesolimbic and nigrostriatal dopaminergic pathways, in that levels of DA in nucleus accumbens and striatum were likewise reduced by Ro60-0175 and elevated, though less markedly, by SB206,553. In line with the above findings, Ro60-0175 dose-dependently decreased the firing rate of ventrotegmental dopaminergic and locus coeruleus (LC) adrenergic perikarya, whereas their activity was dose-dependently enhanced by SB206,553. Furthermore, SB206,553 transformed the firing pattern of ventrotegmental dopaminergic neurons into a burst mode. In contrast to SB206,553, MDL100,907 had little affect on the firing rate of dopaminergic or adrenergic neurons. In conclusion, as compared to 5-HT2A and 5-HT2B receptors, 5-HT2C receptors exert a tonic, suppressive influence on the activity of mesocortical — as well as mesolimbic and nigrostriatal — dopaminergic pathways, likely via indirect actions expressed at the level of their cell bodies. Frontocortical adrenergic, but not serotonergic, transmission is also tonically suppressed by 5-HT2C receptors. Synapse 36:205–221, 2000. © 2000 Wiley-Liss, Inc.

344 citations

Journal ArticleDOI
TL;DR: Electrophysiological and dialysis analyses of the complex and reciprocal pattern of autoand heteroreceptor mediated control of dopaminergic, noradrenergic and serotonergic transmission in the FCX provide a framework for an interpretation of the influence of diverse classes of antidepressant agent upon extracellular levels of dopamine, Noradrenaline and serotonin in FCX.
Abstract: The frontal cortex (FCX) plays a key role in processes that control mood, cognition and motor behaviour, functions which are compromised in depression, schizophrenia and other psychiatric disorders. In this regard, there is considerable evidence that a perturbation of monoaminergic input to the FCX is involved in the pathogenesis of these states. Correspondingly, the modulation of monoaminergic transmission in the FCX and other corticolimbic structures plays an important role in the actions of antipsychotic and antidepressant agents. In order to further understand the significance of monoaminergic systems in psychiatric disorders and their treatment, it is essential to characterize mechanisms underlying their modulation. Within this framework, the present commentary focuses on our electrophysiological and dialysis analyses of the complex and reciprocal pattern of auto- and heteroreceptor mediated control of dopaminergic, noradrenergic and serotonergic transmission in the FCX. The delineation of such interactions provides a framework for an interpretation of the influence of diverse classes of antidepressant agent upon extracellular levels of dopamine, noradrenaline and serotonin in FCX. Moreover, it also generates important insights into strategies for the potential improvement in the therapeutic profiles of antidepressant agents.

247 citations

Journal ArticleDOI
TL;DR: There is a complex pattern of reciprocal autoreceptor and heteroceptor control of monoamine release in the frontal cortex of freely-moving rats using a novel and exceptionally sensitive method of high-performance liquid chromatography coupled to coulometric detection.

210 citations

Journal ArticleDOI
TL;DR: The release rates of glutamate, aspartate, gamma-aminobutyric acid, glycine, 5-hydroxytryptamine and catecholamines, are modified in particular by arousing and stressful stimuli, pain, changes in cardiovascular homeostasis, as well as during opioid withdrawal or the sleep-wake-cycle.

207 citations

References
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Journal ArticleDOI
TL;DR: The distribution of serotonin-1 (5-HT1) receptors in the rat brain was studied by light microscopic quantitative autoradiography and the existence of 'selective' areas allowed a detailed pharmacological characterization of these sites to be made in a more precise manner than has been attained in membrane-binding studies.

1,866 citations

Journal ArticleDOI
01 Jan 1987-Synapse
TL;DR: D dorsal raphe 5‐HT neurons appear highly responsive to 5‐ht1A, but not to 5-HT1B compounds; these findings are discussed with regard to the 5‐ HT receptor subtypes as candidates for the somatodendritic autoreceptor of dorsal raphes neurons.
Abstract: A direct comparison was made of the effects of serotonin 5-HT1A and 5-HT1B selective compounds on the spontaneous firing rate of dorsal raphe serotoninergic neurons in chloral-hydrate-anesthetized rats. Following intravenous administration, the 5-HT1A selective compounds ipsapirone (TVX Q 7821) and LY 165163 potently inhibited single-unit activity in a dose-dependent manner whereas the 5-HT1B selective compounds, m-chlorophenylpiperazine (mCPP) and trifluoromethylphenylpiperazine (TFMPP), displayed only weak or irregular actions. Low microiontophoretic currents of ipsapirone and LY 165163 were also effective in suppressing spontaneous firing; dose-response relationships for the 5-HT1A compounds were indistinguishable from that of 5-HT itself. In contrast, dorsal raphe neurons were only weakly responsive to microiontophoretic application of mCPP and TFMPP; dose-response relationships for the 5-HT1B compounds were significantly displaced from that of 5-HT. In intracellular studies, ipsapirone and LY 165163, when added to the media bathing brain slices, mimicked the actions of 5-HT in hyperpolarizing dorsal raphe cell membranes and decreasing input resistance; however, the maximal effects of the 5-HT1A compounds on these membrane properties exceeded those of 5-HT. In summary, dorsal raphe 5-HT neurons appear highly responsive to 5-HT1A, but not to 5-HT1B compounds; these findings are discussed with regard to the 5-HT receptor subtypes as candidates for the somatodendritic autoreceptor of dorsal raphe neurons.

874 citations


"Serotonin-norepinephrine interactio..." refers background in this paper

  • ...supported by electrophysiological studies showing that 5-HT1A agonists reduce the firing rate of 5-HT neurons (Sprouse and Aghajanian, 1987)....

    [...]

Journal ArticleDOI
TL;DR: Data indicate that the initial effect of PCA or FF administration is the rapid functional release of stored serotonin, which is a reflection of the activity of central serotonin-mediated synapses.

257 citations


"Serotonin-norepinephrine interactio..." refers background in this paper

  • ...The well-documented drug effect of fenfluramine on 5-HT release (Trulson and Jacobs, 1976) was used to elucidate whether the 5-HT1A and 5-HT~B agonists mimic the action of endogenous 5-HT on NE metabolism in the LC....

    [...]

  • ...), known to release 5-HT and to inhibit 5-HT uptake (Trulson and Jacobs, 1976), increased slightly...

    [...]

Journal ArticleDOI
TL;DR: Findings suggest that NE terminals directly innervate 5-HT cells in the dorsal raphe, and a majority of NE-labelled terminals, which formed synaptic specializations, innervated degenerating dendrites.

257 citations