A Comparative Study of the Effects of Selective and Non-Selective 5-HT2 Receptor Subtype Antagonists in Rat and Mouse Models of Anxiety

doi:10.1016/S0028-3908(97)00034-8

Neuropharmacology

Volume 36, Issue 6, June 1997, Pages 793-802

https://doi.org/10.1016/S0028-3908(97)00034-8 Get rights and content

Abstract

Although there is some evidence that compounds acting at 5-HT₂ receptors show anxiolytic activity, little is known about the specific involvement of the different 5-HT₂ receptor subtypes in the modulation of anxiety-related responses. In the present study, the behavioural effects of mianserin, a nonselective 5-HT₂ receptor antagonist, MDL 100,907, a selective 5-HT_2A receptor antagonist, and SB 206553, a selective 5-HT_2B/2C receptor antagonist, were investigated in two rat (the Vogel drinking conflict and the elevated plus-maze tests) and two mouse (i.e. the mouse defense test battery (MDTB) and the light/dark choice test) models of anxiety. Diazepam was used as a positive control. In the Vogel drinking test, mianserin (10 mg/kg) and SB 206553 (3–30 mg/kg), but not MDL 100,907, increased punished responding. Similarly, mianserin (1 mg/kg) and SB 206553 (3–10 mg/kg), but not MDL 100,907, increased entries into the open arms of the elevated plus-maze. These effects are consistent with anxiolytic-like actions of mianserin and SB 206553, although the magnitude of the effects of these two compounds was less than those of diazepam. In addition, in the MDTB, the 5-HT₂ antagonists did not clearly affect the defensive reactions of mice exposed to a rat stimulus and they failed to reverse the avoidance of the illuminated box in the light/dark choice test. These results indicate a lack of anxiolytic-like action of the compounds in mice. These behavioural profiles suggest that blockade of the 5-HT_2A receptor may not reduce anxiety and demonstrate that 5-HT_2B and/or 5-HT_2C receptor subtypes may be primarily involved in the anxiolytic-like effects of mianserin and SB 206553 in rats. © 1997 Elsevier Science Ltd.

Section snippets

Animals

Male Sprague-Dawley rats (Iffa Credo, L'Arbresle and Charles River France, Saint-Aubin-les-Elbeuf) weighing 180–230 g at time of testing were used in the Vogel drinking and the elevated plus-maze tests. Male Long Evans rats (400–500 g) (Iffa Credo) were used as threat stimulus in the MDTB. BALB/c mice (7 weeks old) and male Swiss mice (10 weeks old) (both provided by Iffa Credo) were used in the light/dark test and the MDTB, respectively. Rats were housed in groups of eight, BALB/c mice in

Vogel drinking test

Table 1 shows that mianserin (K = 17.98, p < 0.01) at 10 mg/kg and SB 206553 (K = 13.14, p < 0.05) at 3, 10 and 30 mg/kg significantly increased the number of punished licks. However, the effects of the benzodiazepine diazepam (5 mg/kg) were greater. Although the effect of MDL 100,907 did not reach statistical significance, a tendency to an increase was observed at 1 mg/kg.

Elevated plus-maze test

Fig. 1 shows that mianserin at 1 mg/kg and SB 206553 at 3 mg/kg significantly increased both the percentage of time spent

Discussion

The results of the present study revealed that the non-selective 5-HT₂ receptor antagonist mianserin and the selective 5-HT_2B/2C receptor antagonist SB 206553, but not the 5-HT_2A receptor antagonist MDL 100,907, displayed behavioural profiles in rats which are consistent with an anxiolytic-like action. By contrast, none of the compounds exhibited clear anxiety-reducing effects in the MDTB nor modified significantly the behaviour of mice in the light/dark choice test.

In the Vogel drinking

Acknowledgements

The skilled technical assistance of Carmen Aliaga, Monique Lhermitte, Elisabeth Pillière and Marc Chalus is gratefully acknowledged.

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A Comparative Study of the Effects of Selective and Non-Selective 5-HT2 Receptor Subtype Antagonists in Rat and Mouse Models of Anxiety

Abstract

Section snippets

Animals

Vogel drinking test

Elevated plus-maze test

Discussion

Acknowledgements

Eur. J. Pharmacol.

Trends Pharmacol. Sci.

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Neuropharmacology

Pharmacol. Ther.

Neuropharmacology

Pharmacol. Biochem. Behav.

Neuropharmacology

J. Pharmacol. Toxicol. Meth.

Pharmacol. Biochem. Behav.

Psychiat. Res.

Pharmacol. Biochem. Behav.

FEBS Lett.

Behav. Process.

Brain Res. Bull.

Behav. Brain Res.

J. Neurosci. Meth.

Eur. J. Pharmacol.

Pharmacol. Biochem. Behav.

Eur. J. Pharmacol.

Psychiat. Res.

Neurosci. Biobehav. Rev.

Pharmacol. Biochem. Behav.

Novel discriminatory ligands for 5-HT2B receptors

Behav. Brain Res.

The influence of ritanserin, a serotonin antagonist, in anxiety disorders: a double-blind placebo-controlled study versus lorazepam

Pharmacopsychiatry

Serotonin function in anxietyII. Effects of the serotonin agonist MCPP in panic disorder patients and healthy subjects

Psychopharmacology

An ethological analysis of the effects of chlordiazepoxide and bretazenil (Ro 16-6028) in the murine elevated plus-maze

Behav. Pharmacol.

Ethological evaluation of the effects of acute and chronic buspirone treatment in the murine elevated plus-maze test: comparison with haloperidol

Psychopharmacology

Behavioral and 5-HT antagonist effects of ritanserin: a pure and selective antagonist of LSD discrimination in rat

Psychopharmacology

Actions of buspirone in a putative model of anxiety in the mouse

J. Pharm. Pharmacol.

A Comparative Study of the Effects of Selective and Non-Selective 5-HT₂ Receptor Subtype Antagonists in Rat and Mouse Models of Anxiety

Novel discriminatory ligands for 5-HT_2B receptors