Effects of repeated treatment with 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on the autoregulatory control of dorsal raphe 5-HT neuronal firing and cortical 5-HT release

Kidd, Emma Jane; Garratt, Jeni C.; Marsden, C.A.

doi:10.1016/0014-2999(91)90675-g

Cited by 23 publications

(9 citation statements)

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“…The caudate nucleus also represents an important projection field for serotonergic neurons located in the raphe nuclei [162,168]. Serotonergic neurons of the raphe nuclei form extended projections to the cerebral cortex [71,94,146] and the raphe-cortical 5-HT neurons mediate an inhibition in the cortical neural network [116,154]. In many cases, forebrain structures that receive serotonergic innervations from the raphe nuclei send neuronal inputs back to the midbrain serotonergic nuclei [165].…”

Section: External Connections Of the Raphe Nuclei With Other Brain Stmentioning

confidence: 99%

“…Presynaptic interaction may also exist between 5-HT 1A and 5-HT 2 receptor functions in the raphe nuclei and 5-HT 2 receptor activation which facilitates presynaptic 5-HT 1A receptor function [94]. Moreover, after repeated administration of the 5-HT 2 receptor agonist DOI, 5-HT 2 receptors are down regulated and somatodendritic 5-HT 1A receptor inhibition on 5-HT neuronal firing is attenuated [94].…”

Section: -Ht 2 Receptor-mediated 5-ht Release In the Raphe Nucleimentioning

confidence: 99%

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The Pharmacology of the Neurochemical Transmission in the Midbrain Raphe Nuclei of the Rat

Hársing

2006

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3 H]5-HT taken up by raphe tissue indicated various pools where the neurotransmitter release may originate from these stores differed both in size and rate constant. 5-HT release originates not only from vesicles but also from cytoplasmic stores via a transporter-dependent exchange process establishing synaptic and non-synaptic neurochemical transmission in the serotonergic somatodendritic area. Manipulation of 5-HT transporter function modulates extracellular 5-HT concentrations in the raphe nuclei: of the SSRIs, fluoxetine was found 5-HT releaser, whereas citalopram did not exhibit this effect. Serotonergic projection neurons in the raphe nuclei possess inhibitory 5-HT 1A and 5-HT 1B/1D receptors and facilitatory 5-HT 3 receptors, which regulate 5-HT release in an opposing fashion. This observation indicates that somatodendritic 5-HT release in the raphe nuclei is under the control of several 5-HT homoreceptors. 5-HT 7 receptors located on glutamatergic axon terminals indirectly inhibit 5-HT release by reducing glutamatergic facilitation of serotonergic projection neurons. An opposite regulation of glutamatergic axon terminals was also found by involvement of the inhibitory 5-HT 7 and the stimulatory 5-HT 2 receptors as these receptors inhibit and stimulate glutamate release in raphe slice preparation, respectively, Furthermore, postsynaptic 5-HT 1B/1D heteroreceptors interact with release of GABA in inhibitory fashion in raphe GABAergic interneurons. Serotonergic projection neurons also possess glutamate and GABA heteroreceptors; NMDA and AMPA receptors release 5-HT, whereas both GABA A and GABA B receptors inhibit somatodendritic 5-HT release. Evidence was found for reciprocal interactions between serotonergic and glutamatergic as well as serotonergic and GABAergic innervations in the raphe nuclei. Serotonergic neurons in the raphe nuclei also receive noradrenergic innervation arising from the locus coeruleus and alpha-1 and alpha-2 adrenoceptors inhibited [3 H]5-HT release in our experimental conditions. The close relation between 5-HT transporter and release-mediating 5-HT autoreceptors was also shown by addition of L-deprenyl, a drug possessing inhibition of type B monoamine oxidase and 5-HT reuptake. L-Deprenyl selectively desensitizes 5-HT 1B but not 5-HT 1A receptors and these effects are not related to inhibition of 5-HT metabolism but rather to inhibition of 5-HT transporter.

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Section: External Connections Of the Raphe Nuclei With Other Brain Stmentioning

confidence: 99%

Section: -Ht 2 Receptor-mediated 5-ht Release In the Raphe Nucleimentioning

confidence: 99%

The Pharmacology of the Neurochemical Transmission in the Midbrain Raphe Nuclei of the Rat

Hársing

2006

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“…Beside serotonergic projection neurons, DRN also contains GABAergic interneurons as well as numerous noradrenergic and glutamatergic axon terminals. Morphological and functional observations confirmed the existence of a glutamatergic pathway arising from the median prefrontal cortex (Behzadi et al, 1990;Hajos et al, 1998) whereas serotonergic neurons of DRN form extended projection to the cerebral cortex (Kidd et al, 1991;Sesack et al, 1989). Thus, the raphe-cortical serotonergic and the cortico-raphe glutamatergic projections establish a long-axon neuronal loop between these two brain structures.…”

Section: Introductionmentioning

confidence: 63%

The synaptic and nonsynaptic glycine transporter type-1 inhibitors Org-24461 and NFPS alter single neuron firing rate in the rat dorsal raphe nucleus

Papp

Jurányi

Nagymajtényi

et al. 2008

Neurochemistry International

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Single neuron firing rate was recorded from dorsal raphe nucleus of anesthetized rats. The firing rate of raphe neurons varied from 4 to 8 discharge per second before drug administration and this neuronal activity was decreased by L-701,324 (2 mg/kg i.v. injection), a competitive antagonist of glycineB binding site of N-methyl-D-aspartate (NMDA) receptors. The glycine transporter type-1 (GlyT1) antagonists Org-24461 (10 mg/kg i.v.) and NFPS (3 mg/kg i.v.) reversed the inhibitory effect of L-701,324 on single neuron activity recorded from dorsal raphe nucleus of the rat. Org-24461 and NFPS both tended to increase the raphe neuronal firing rate also when given alone but their effect was not significant. This finding serves further evidence that glutamate released from axon terminals of the cortico-striatal projection neurons stimulates serotonergic neurons in the raphe nuclei and this effect is mediated at least in part by postsynaptic NMDA receptors. Thus, GlyT1 inhibitors are able to reverse the hypofunctional state of NMDA receptors, suggesting that these drugs may have beneficial therapeutic effects in neurological and psychiatric disorders characterized with impaired NMDA receptor-mediated transmission.

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“…(1990) have shown that chronic administration of the 5‐HT 2 receptor antagonist ritanserin, a treatment regimen that decreases the number of 5‐HT 2 receptor binding sites in cortex, decreased the inhibitory effect of the 5‐HT 1A agonist receptor 8‐OH‐DPAT on 5‐HT release. Moreover, repeated administration of the 5‐HT 2 receptor agonist, DOI, which also downregulates 5‐HT 2 receptors in the cortex, attenuated the 5‐HT 1A receptor‐mediated inhibitory action of 8‐OH‐DPAT on DRN 5‐HT neuronal firing ( Kidd et al ., 1991 ). 8‐OH‐DPAT is known to inhibit 5‐HT neuronal firing via a feedback loop, most likely extending from the cortex ( Blier & de Montigny, 1987 ; Ceci et al ., 1994 ).…”

Section: Discussionmentioning

confidence: 99%

Electrophysiological examination of the effects of sustained flibanserin administration on serotonin receptors in rat brain

Rueter

Blier

1999

British J Pharmacology

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1 5-HT 1A receptor agonists have proven to be eective antidepressant medications, however they suer from a signi®cant therapeutic lag before depressive symptoms abate. Flibanserin is a 5-HT 1A receptor agonist and 5-HT 2A receptor antagonist developed to possibly induce a more rapid onset of antidepressant action through its preferential postsynaptic 5-HT 1A receptor agonism. 2 Flibanserin antagonized the eect of microiontophoretically-applied DOI in the medial prefrontal cortex (mPFC) following 2 days of administration, indicating antagonism of postsynaptic 5-HT 2A receptors. This reduction in the eect of locally-applied DOI was no longer present following 7-day¯ibanserin administration. 3 Two-day¯ibanserin administration only marginally reduced the ®ring activity of dorsal raphe (DRN) 5-HT neurons. Following 7 days of administration, 5-HT neuronal ®ring activity had returned to normal and the somatodendritic 5-HT 1A autoreceptors were desensitized. 4 The responsiveness of postsynaptic 5-HT 1A receptors located on CA 3 hippocampus pyramidal neurons and mPFC neurons, examined using microiontophoretically-applied 5-HT and gepirone, was unchanged following a 7-day¯ibanserin treatment. 5 As demonstrated by the ability of the 5-HT 1A receptor antagonist WAY 100635 to selectively increase the ®ring of hippocampal neurons in 2-and 7-day treated rats,¯ibanserin enhanced the tonic activation of postsynaptic 5-HT 1A receptors in this brain region. 6 The results suggest that¯ibanserin could be a therapeutically useful compound putatively endowed with a more rapid onset of antidepressant action.

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Effects of repeated treatment with 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on the autoregulatory control of dorsal raphe 5-HT neuronal firing and cortical 5-HT release

Cited by 23 publications

References 38 publications

The Pharmacology of the Neurochemical Transmission in the Midbrain Raphe Nuclei of the Rat

The Pharmacology of the Neurochemical Transmission in the Midbrain Raphe Nuclei of the Rat

The synaptic and nonsynaptic glycine transporter type-1 inhibitors Org-24461 and NFPS alter single neuron firing rate in the rat dorsal raphe nucleus

Electrophysiological examination of the effects of sustained flibanserin administration on serotonin receptors in rat brain

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