Further pharmacological characterization of 5-HT(2C) receptor agonist-induced inhibition of 5-HT neuronal activity in the dorsal raphe nucleus in vivo.
BACKGROUND AND PURPOSE: Recent experiments using non-selective 5-hydroxytryptamine (5-HT)(2C) receptor agonists including WAY 161503 suggested that midbrain 5-HT neurones are under the inhibitory control of 5-HT(2C) receptors, acting via neighbouring gamma-aminobutyric acid (GABA) neurones. The pre...
| Автори: | , , |
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| Формат: | Journal article |
| Мова: | English |
| Опубліковано: |
2009
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| _version_ | 1826260740574543872 |
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| author | Quérée, P Peters, S Sharp, T |
| author_facet | Quérée, P Peters, S Sharp, T |
| author_sort | Quérée, P |
| collection | OXFORD |
| description | BACKGROUND AND PURPOSE: Recent experiments using non-selective 5-hydroxytryptamine (5-HT)(2C) receptor agonists including WAY 161503 suggested that midbrain 5-HT neurones are under the inhibitory control of 5-HT(2C) receptors, acting via neighbouring gamma-aminobutyric acid (GABA) neurones. The present study extended this pharmacological characterization by comparing the actions of WAY 161503 with the 5-HT(2C) receptor agonists, Ro 60-0275 and 1-(3-chlorophenyl) piperazine (mCPP), as well as the non-selective 5-HT agonist lysergic acid diethylamide (LSD) and the 5-HT releasing agent 3,4-methylenedioxymethamphetamine (MDMA). EXPERIMENTAL APPROACH: 5-HT neuronal activity was measured in the dorsal raphe nucleus (DRN) using extracellular recordings in anaesthetized rats. The activity of DRN GABA neurones was assessed using double-label immunohistochemical measurements of Fos and glutamate decarboxylase (GAD). KEY RESULTS: Ro 60-0175, like WAY 161503, inhibited 5-HT neurone firing, and the 5-HT(2C) antagonist SB 242084 reversed this effect. mCPP also inhibited 5-HT neurone firing ( approximately 60% neurones) in a SB 242084-reversible manner. LSD inhibited 5-HT neurone firing; however, this effect was not altered by either SB 242084 or the 5-HT(2A/C) receptor antagonist ritanserin but was reversed by the 5-HT(1A) receptor antagonist WAY 100635. Similarly, MDMA inhibited 5-HT neurone firing in a manner reversible by WAY 100635, but not SB 242084 or ritanserin. Finally, both Ro 60-0275 and mCPP, like WAY 161503, increased Fos expression in GAD-positive DRN neurones. CONCLUSIONS AND IMPLICATIONS: These data strengthen the hypothesis that midbrain 5-HT neurones are under the inhibitory control of 5-HT(2C) receptors, and suggest that the 5-HT(2C) agonists Ro 60-0175, mCPP and WAY 161503, but not LSD or MDMA, are useful probes of the mechanism(s) involved. |
| first_indexed | 2024-03-06T19:10:30Z |
| format | Journal article |
| id | oxford-uuid:169d8e33-8aff-4078-8afa-df65b9f8fada |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:10:30Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:169d8e33-8aff-4078-8afa-df65b9f8fada2022-03-26T10:32:21ZFurther pharmacological characterization of 5-HT(2C) receptor agonist-induced inhibition of 5-HT neuronal activity in the dorsal raphe nucleus in vivo.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:169d8e33-8aff-4078-8afa-df65b9f8fadaEnglishSymplectic Elements at Oxford2009Quérée, PPeters, SSharp, T BACKGROUND AND PURPOSE: Recent experiments using non-selective 5-hydroxytryptamine (5-HT)(2C) receptor agonists including WAY 161503 suggested that midbrain 5-HT neurones are under the inhibitory control of 5-HT(2C) receptors, acting via neighbouring gamma-aminobutyric acid (GABA) neurones. The present study extended this pharmacological characterization by comparing the actions of WAY 161503 with the 5-HT(2C) receptor agonists, Ro 60-0275 and 1-(3-chlorophenyl) piperazine (mCPP), as well as the non-selective 5-HT agonist lysergic acid diethylamide (LSD) and the 5-HT releasing agent 3,4-methylenedioxymethamphetamine (MDMA). EXPERIMENTAL APPROACH: 5-HT neuronal activity was measured in the dorsal raphe nucleus (DRN) using extracellular recordings in anaesthetized rats. The activity of DRN GABA neurones was assessed using double-label immunohistochemical measurements of Fos and glutamate decarboxylase (GAD). KEY RESULTS: Ro 60-0175, like WAY 161503, inhibited 5-HT neurone firing, and the 5-HT(2C) antagonist SB 242084 reversed this effect. mCPP also inhibited 5-HT neurone firing ( approximately 60% neurones) in a SB 242084-reversible manner. LSD inhibited 5-HT neurone firing; however, this effect was not altered by either SB 242084 or the 5-HT(2A/C) receptor antagonist ritanserin but was reversed by the 5-HT(1A) receptor antagonist WAY 100635. Similarly, MDMA inhibited 5-HT neurone firing in a manner reversible by WAY 100635, but not SB 242084 or ritanserin. Finally, both Ro 60-0275 and mCPP, like WAY 161503, increased Fos expression in GAD-positive DRN neurones. CONCLUSIONS AND IMPLICATIONS: These data strengthen the hypothesis that midbrain 5-HT neurones are under the inhibitory control of 5-HT(2C) receptors, and suggest that the 5-HT(2C) agonists Ro 60-0175, mCPP and WAY 161503, but not LSD or MDMA, are useful probes of the mechanism(s) involved. |
| spellingShingle | Quérée, P Peters, S Sharp, T Further pharmacological characterization of 5-HT(2C) receptor agonist-induced inhibition of 5-HT neuronal activity in the dorsal raphe nucleus in vivo. |
| title | Further pharmacological characterization of 5-HT(2C) receptor agonist-induced inhibition of 5-HT neuronal activity in the dorsal raphe nucleus in vivo. |
| title_full | Further pharmacological characterization of 5-HT(2C) receptor agonist-induced inhibition of 5-HT neuronal activity in the dorsal raphe nucleus in vivo. |
| title_fullStr | Further pharmacological characterization of 5-HT(2C) receptor agonist-induced inhibition of 5-HT neuronal activity in the dorsal raphe nucleus in vivo. |
| title_full_unstemmed | Further pharmacological characterization of 5-HT(2C) receptor agonist-induced inhibition of 5-HT neuronal activity in the dorsal raphe nucleus in vivo. |
| title_short | Further pharmacological characterization of 5-HT(2C) receptor agonist-induced inhibition of 5-HT neuronal activity in the dorsal raphe nucleus in vivo. |
| title_sort | further pharmacological characterization of 5 ht 2c receptor agonist induced inhibition of 5 ht neuronal activity in the dorsal raphe nucleus in vivo |
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