Control of dorsal raphé 5-HT function by multiple 5-HT1 autoreceptors: parallel purposes or pointless plurality?

Stamford, Jonathan A.; Davidson, Charles S.; McLaughlin, Daniel P.; Hopwood, Sarah E.

doi:10.1016/s0166-2236(00)01631-3

Cited by 128 publications

(63 citation statements)

References 51 publications

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“…Despite a high density of 5-HT 1B receptors in the SNr, they are observed predominantly on striatonigral GABAergic terminals from the striatum rather than on serotonergic terminals (Boschert et al, 1994;Sari et al, 1999). It appears that 5-HT release in the SNr is not regulated by 5-HT receptors; this is not the case in the raphe nuclei where a plurality of 5-HT receptors perform autoreceptor-like functions (Stamford et al, 2000;Hopwood and Stamford, 2001). H 3 R-mediated control of 5-HT release in SNr may provide a substitute mechanism for presynaptic inhibition of 5-HT release.…”

Section: H 3 R Control Of 5-ht Release In the Snrmentioning

confidence: 97%

Histamine H₃Receptors Inhibit Serotonin Release in Substantia Nigra Pars Reticulata

et al. 2004

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Section: H 3 R Control Of 5-ht Release In the Snrmentioning

confidence: 97%

Histamine H₃Receptors Inhibit Serotonin Release in Substantia Nigra Pars Reticulata

et al. 2004

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“…The release-inhibitory 5-HT 1A receptors are located on the somatodendritic part of 5-HT neurons and control the bulky, possibly non-synaptic release of 5-HT [115,117]. It has been suggested that the multiple 5-HT 1 receptormediated mechanisms, that control 5-HT function in the raphe nuclei, open new therapeutic possibilities for psychiatric disorders [151]. Using midbrain slice preparations containing raphe nuclei, it was possible to demonstrate the inhibitory effects of various 5-HT 1 receptor subtypes on 5-HT release in vitro [9].…”

Section: Compartmentalization Of [ 3 H]5-ht Taken Up Into Raphe Nuclementioning

confidence: 99%

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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“…Dysregulation of DRN serotonergic neurotransmission has been implicated in many psychiatric illnesses, such as anxiety and depressive disorders (Graeff et al, 1996;Underwood et al, 1999;Lowry et al, 2008). Additionally, enhancement of DRN serotonin (5-HT) release has been proposed to be responsible for the actions of some antidepressants (Stamford et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Elucidation of The Behavioral Program and Neuronal Network Encoded by Dorsal Raphe Serotonergic Neurons

Urban

Zhu

Marcinkiewcz

et al. 2015

Neuropsychopharmacol

125

100

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Elucidating how the brain's serotonergic network mediates diverse behavioral actions over both relatively short (minutes-hours) and long period of time (days-weeks) remains a major challenge for neuroscience. Our relative ignorance is largely due to the lack of technologies with robustness, reversibility, and spatio-temporal control. Recently, we have demonstrated that our chemogenetic approach (eg, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)) provides a reliable and robust tool for controlling genetically defined neural populations. Here we show how short-and long-term activation of dorsal raphe nucleus (DRN) serotonergic neurons induces robust behavioral responses. We found that both short-and long-term activation of DRN serotonergic neurons induce antidepressant-like behavioral responses. However, only short-term activation induces anxiogenic-like behaviors. In parallel, these behavioral phenotypes were associated with a metabolic map of whole brain network activity via a recently developed non-invasive imaging technology DREAMM (DREADD Associated Metabolic Mapping). Our findings reveal a previously unappreciated brain network elicited by selective activation of DRN serotonin neurons and illuminate potential therapeutic and adverse effects of drugs targeting DRN neurons.

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Control of dorsal raphé 5-HT function by multiple 5-HT1 autoreceptors: parallel purposes or pointless plurality?

Cited by 128 publications

References 51 publications

Histamine H₃Receptors Inhibit Serotonin Release in Substantia Nigra Pars Reticulata

Histamine H₃Receptors Inhibit Serotonin Release in Substantia Nigra Pars Reticulata

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

Elucidation of The Behavioral Program and Neuronal Network Encoded by Dorsal Raphe Serotonergic Neurons

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Control of dorsal raphé 5-HT function by multiple 5-HT1 autoreceptors: parallel purposes or pointless plurality?

Cited by 128 publications

References 51 publications

Histamine H3Receptors Inhibit Serotonin Release in Substantia Nigra Pars Reticulata

Histamine H3Receptors Inhibit Serotonin Release in Substantia Nigra Pars Reticulata

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

Elucidation of The Behavioral Program and Neuronal Network Encoded by Dorsal Raphe Serotonergic Neurons

Contact Info

Product

Resources

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Histamine H₃Receptors Inhibit Serotonin Release in Substantia Nigra Pars Reticulata

Histamine H₃Receptors Inhibit Serotonin Release in Substantia Nigra Pars Reticulata