Acute selective serotonin reuptake inhibitors regulate the dorsal raphe nucleus causing amplification of terminal serotonin release

Triptans are 5-HT1 receptor agonists used as anti-migraine drugs. They act primarily on meningeal blood vessels and on trigeminovascular afferents, but they may also exert central effects. We studied the regional effects of acute and chronic treatment with sumatriptan or zolmitriptan on the rate of serotonin (5-HT) synthesis in the rat brain, using the α-14C-methyl-L-tryptophan quantitative autoradiographic method. Sumatriptan at low (300 μg/kg, s.c.) and high (1 mg/kg) doses, as well as zolmitriptan (100 μg/kg), acutely decreased (15-40%, P < 0.05-0.001) 5-HT synthetic rate in many brain regions, including the dorsal raphe nucleus. Chronically, sumatriptan (21 days, approximately 300 μg/kg per day via osmotic minipumps) induced significant increases in the 5-HT synthesis rate in many projection areas but had no effect in the dorsal raphe nucleus. The acute effects on 5-HT synthesis rate would be compatible with activation of 5-HT1 autoreceptors that inhibit serotonin release. In contrast, the increased 5-HT synthesis rate observed after chronic sumatriptan might possibly result from a down-regulation/desensitization of 5-HT1 receptors and/or unmasking of excitatory triptan-sensitive 5-HT receptors. Overall, the present findings indicate that not only zolmitriptan but also sumatriptan affect brain serotonergic neurotransmission.

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Alteration of Serotonin Release in the Guinea Pig Orbito-Frontal Cortex by Selective Serotonin Reuptake Inhibitors Relevance to Treatment of Obsessive-Compulsive Disorder

Neuropsychopharmacology ◽

10.1016/0893-133x(95)00045-f ◽

1995 ◽

Vol 13 (2) ◽

pp. 117-127 ◽

Cited By ~ 82

Author(s):

M El Mansari

Keyword(s):

Guinea Pig ◽

Frontal Cortex ◽

Obsessive Compulsive Disorder ◽

Serotonin Reuptake ◽

Selective Serotonin Reuptake Inhibitors ◽

Serotonin Release ◽

Serotonin Reuptake Inhibitors ◽

Selective Serotonin ◽

Obsessive Compulsive ◽

Compulsive Disorder

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Somatosensory regulation of serotonin release in the central nucleus of the amygdala is mediated via corticotropin releasing factor and gamma-aminobutyric acid in the dorsal raphe nucleus

The Journal of Physiological Sciences ◽

10.1007/s12576-016-0498-4 ◽

2016 ◽

Vol 67 (6) ◽

pp. 689-698 ◽

Cited By ~ 1

Author(s):

Ryota Tokunaga ◽

Rie Shimoju ◽

Hideshi Shibata ◽

Mieko Kurosawa

Keyword(s):

Dorsal Raphe Nucleus ◽

Dorsal Raphe ◽

Serotonin Release ◽

Raphe Nucleus ◽

Corticotropin Releasing Factor ◽

Aminobutyric Acid ◽

Central Nucleus ◽

Gamma Aminobutyric Acid ◽

Dorsal Raphé

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GABAergic modulation of serotonergic neurons in the dorsal raphe nucleus

Reviews in the Neurosciences ◽

10.1515/revneuro-2018-0014 ◽

2019 ◽

Vol 30 (3) ◽

pp. 289-303 ◽

Cited By ~ 9

Author(s):

Fabiola Hernández-Vázquez ◽

Julieta Garduño ◽

Salvador Hernández-López

Keyword(s):

Stress Responses ◽

Dorsal Raphe Nucleus ◽

Morphological Characteristics ◽

Dorsal Raphe ◽

Serotonin Release ◽

Gabaergic Neurons ◽

Raphe Nucleus ◽

Serotonergic Neurons ◽

Brain Areas ◽

Dorsal Raphé

Abstract The dorsal raphe nucleus (DRN), located in the brainstem, is involved in several functions such as sleep, temperature regulation, stress responses, and anxiety behaviors. This nucleus contains the largest population of serotonin expressing neurons in the brain. Serotonergic DRN neurons receive tonic γ-aminobutyric acid (GABA)inhibitory inputs from several brain areas, as well as from interneurons within the same nucleus. Serotonergic and GABAergic neurons in the DRN can be distinguished by their size, location, pharmacological responses, and electrophysiological properties. GABAergic neurons regulate the excitability of DRN serotonergic neurons and the serotonin release in different brain areas. Also, it has been shown that GABAergic neurons can synchronize the activity of serotonergic neurons across functions such as sleep or alertness. Moreover, dysregulation of GABA signaling in the DRN has been linked to psychiatric disorders such as anxiety and depression. This review focuses on GABAergic transmission in the DRN. The interaction between GABAergic and serotonergic neurons is discussed considering some physiological implications. Also, the main electrophysiological and morphological characteristics of serotonergic and GABAergic neurons are described.

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