Are 5-HT2 antagonists endowed with anxiolytic properties in rodents?

Stutzmann, Jean‐Marie; Eon, B.; Darche, F.; Lucas, M.; Rataud, J.; Piot, O.; Blanchard, Jean‐Charles; Laduron, Pierre M.

doi:10.1016/0304-3940(91)90747-h

Cited by 38 publications

(6 citation statements)

References 19 publications

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“…For example, the widely used 5-HT 2 receptor blocker ritanserin (Leysen et al 1986;Leysen 2004) has been found to produce results ranging from anxiolysis (Ceulemans et al 1985;Griez et al 1988;Hensman et al 1991), through no effect (Den Boer and Westenberg 1990), to anxiogenesis (Guimarães et al 1997) in experimental and/or clinical anxiety. Similarly, systemic administration of selective and nonselective 5-HT 2 receptor antagonists in animal models of anxiety has been reported to display anxiolytic-like effects (Critchley and Handley 1987;Tomkins et al 1990;Stutzmann et al 1991;Wright et al 1992;Kennett et al 1994;Cervo and Samanin 1995;Griebel et al 1997a;Jones et al 2002;Martin et al 2002;Nic Dhonnchadha et al 2003), no effect (Chaouloff et al 1997;Griebel et al 1997b;Setem et al 1999;Martin et al 2002), and even anxiogenic-like effects (Pellow et al 1987). Although these behavioral findings may depend at least partially on the selectivity for 5-HT 2 receptor subtypes, variation in dose range, behavioral task, different types of anxiety disorder, and other procedural differences, the precise reasons for such discrepancies remain unclear.…”

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confidence: 96%

Behavioral effects of systemically administered MK-212 are prevented by ritanserin microinfusion into the basolateral amygdala of rats exposed to the elevated plus-maze

et al. 2005

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Section: Introductionmentioning

confidence: 96%

Behavioral effects of systemically administered MK-212 are prevented by ritanserin microinfusion into the basolateral amygdala of rats exposed to the elevated plus-maze

et al. 2005

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“…However, anxiolytic-like effects of 5-HT 3 receptor antagonists are variable, test dependent and weak (Barrett and Gleeson 1991;Cervo and Samanin 1995;Griebel 1995;Gaster and King 1997;Smith et al 1999). A role for 5-HT 2A receptors in the modulation of anxiety has also been evoked, but there is comparatively little evidence that blockade of 5-HT 2A receptors is associated with anxiolytic-like effects (Stutzmann et al 1991;Chaouloff et al 1997;Griebel et al 1997;Mora et al 1997;Sánchez and Mørk 1999). Interestingly, it was recently suggested that activation of 5-HT 2B receptors may reduce anxiety (Kennett et al 1996a(Kennett et al , 1998Duxon et al 1997), but this contention remains to be confirmed with genuinely selective agonists.…”

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confidence: 96%

The selective serotonin (5-HT)1A receptor ligand, S15535, displays anxiolytic-like effects in the social interaction and Vogel models and suppresses dialysate levels of 5-HT in the dorsal hippocampus of freely-moving rats

et al. 2000

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confidence: 99%

“…Selective and nonselective 5-HT 2C receptor antagonists reduce anxiety-like behavior in several animal models of anxiety (Stutzmann et al, 1991;Kennett et al, 1995;Griebel et al, 1997). For example, SB 242084 [6-chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxyamide dihydrochloride], a potent and selective 5-HT 2C receptor antagonist, is anxiolytic in the social interaction test and the Geller-Seifter conflict test of anxiety (Kennett et al, 1997).…”

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5-Hydroxytryptamine2C Receptor Contribution to m-Chlorophenylpiperazine and N-Methyl-β-carboline-3-carboxamide-Induced Anxiety-Like Behavior and Limbic Brain Activation

Hackler¹,

Turner²,

Gresch³

et al. 2007

The Journal of Pharmacology and Experimental Therapeutics

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Activation of 5-hydroxytryptamine2C (5-HT 2C ) receptors by the 5-HT 2 receptor agonist m-chlorophenylpiperazine (m-CPP) elicits anxiety in humans and anxiety-like behavior in animals. We compared the effects of m-CPP with the anxiogenic GABA A receptor inverse agonist N-methyl-␤-carboline-3-carboxamide (FG-7142) on both anxiety-like behavior and regional brain activation using functional magnetic resonance imaging (fMRI) in the rat. We also determined whether the selective 5-HT 2C receptor antagonist SB 242084 [6-chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxyamide dihydrochloride] would blunt m-CPP or FG-7142-induced neuronal activation. Both m-CPP (3 mg/kg i.p.) and FG-7142 (10 mg/kg i.p.) elicited anxiety-like behavior when measured in the social interaction test, and pretreatment with SB 242084 (1 mg/kg i.p.) completely blocked the behavioral effects of both anxiogenic drugs. Regional brain activation in vivo in response to anxiogenic drug challenge was determined by blood oxygen level-dependent (BOLD) fMRI using a powerful 9.4T magnet. Region of interest analyses revealed that m-CPP and FG-7142 significantly increased BOLD signals in brain regions that have been linked to anxiety, including the amygdala, dorsal hippocampus, and medial hypothalamus. These BOLD signal increases were blocked by pretreatment with SB 242084. In contrast, injection of m-CPP and FG-7142 resulted in BOLD signal decreases in the medial prefrontal cortex that were not blocked by SB 242084. In conclusion, the brain activation signals produced by anxiogenic doses of both m-CPP and FG-7142 are mediated at least partially by the 5-HT 2C receptor, indicating that this receptor is a key component in anxiogenic neural circuitry.The 5-hydroxytryptamine 2C (5-HT 2C ) receptor has been implicated in mood and anxiety disorders and is a target for development of novel anxiolytic drugs (Wood, 2003). Selective and nonselective 5-HT 2C receptor antagonists reduce anxiety-like behavior in several animal models of anxiety (Stutzmann et al., 1991;Kennett et al., 1995;Griebel et al., 1997). (Charney et al., 1987;Lowy and Meltzer, 1988;Kahn and Wetzler, 1991;Gatch, 2003;de Mello Cruz et al., 2005). For example, m-CPP administration to mice resulted in less time spent on the open arms of an elevated plus maze (Benjamin et al., 1990), and in rats, anxiety-like behavior has been reported in the This study was supported by National Institutes of Health Grants T32 GM07628, RO1 MH34007, and R01 EB02326 and a predoctoral fellowship from the PhRMA foundation (to E.A.H.).Article, publication date, and citation information can be found at http://jpet.aspetjournals.org. doi:10.1124/jpet.106.113357. 2C , 5-hydroxytryptamine2C; m-CPP, m-chlorophenylpiperazine; FG-7142, N-methyl-␤-carboline-3-carboxamide; SB 242084, 6-chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxyamide dihydrochloride; fMRI, functional magnetic resonance imaging; BOLD, blood oxygen level-dependent;...

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Are 5-HT2 antagonists endowed with anxiolytic properties in rodents?

Cited by 38 publications

References 19 publications

Behavioral effects of systemically administered MK-212 are prevented by ritanserin microinfusion into the basolateral amygdala of rats exposed to the elevated plus-maze

Behavioral effects of systemically administered MK-212 are prevented by ritanserin microinfusion into the basolateral amygdala of rats exposed to the elevated plus-maze

The selective serotonin (5-HT)1A receptor ligand, S15535, displays anxiolytic-like effects in the social interaction and Vogel models and suppresses dialysate levels of 5-HT in the dorsal hippocampus of freely-moving rats

5-Hydroxytryptamine2C Receptor Contribution to m-Chlorophenylpiperazine and N-Methyl-β-carboline-3-carboxamide-Induced Anxiety-Like Behavior and Limbic Brain Activation

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