Further pharmacological characterization of 5-HT(2C) receptor agonist-induced inhibition of 5-HT neuronal activity in the dorsal raphe nucleus in vivo.
P Quérée, S Peters, T Sharp
British Journal of Pharmacology November 2009 DOI: 10.1111/j.1476-5381.2009.00406.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study using extracellular recordings and immunohistochemistry in rats Peer reviewed |
|---|---|
| Population | Anaesthetized rats |
| Interventions | WAY 161503 Ro 60-0175 mCPP LSD MDMA SB 242084 ritanserin WAY 100635 |
| Measures | extracellular recordings of 5-HT neuronal activity, double-label immunohistochemical measurements of Fos and glutamate decarboxylase (GAD) |
| Topics | Serotonin |
| Key findings | The 5-HT2C agonists Ro 60-0175, mCPP, and WAY 161503 inhibited 5-HT neuron firing in a manner reversed by the 5-HT2C antagonist SB 242084 and increased Fos in GABA neurons, whereas LSD and MDMA inhibited firing via 5-HT1A receptors. The authors argue these data strengthen the hypothesis that midbrain 5-HT neurons are under inhibitory control of 5-HT2C receptors acting through neighbouring GABA neurons. |
Abstract
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). 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). 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. 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.
Comparable studies
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| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 5
- LSD's rapid antidepressant effects are modulated by 5-HT2B receptors. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie July 16, 2025
- LSD: Mechanisms and relevance to the treatment of depression Neuroscience & Biobehavioral Reviews October 10, 2025
- Dorsal Raphe Revisited: A Systems Neuroscience Lens on Psychedelic Drug Action Psychedelic Medicine April 9, 2026
- Positive regulation of raphe serotonin neurons by serotonin 2B receptors. Neuropsychopharmacology June 2018
- Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens. Neuropharmacology January 20, 2011
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