Anxiolytic-like actions of BW 723C86 in the rat Vogel conflict test are 5-HT2B receptor mediated

doi:10.1016/S0028-3908(98)00115-4

Neuropharmacology

Volume 37, Issue 12, 1 December 1998, Pages 1603-1610

https://doi.org/10.1016/S0028-3908(98)00115-4 Get rights and content

Abstract

The 5-HT_2B receptor agonist, BW 723C86 (10, 30 mg/kg i.p. 30 min pre-test), increased the number of punishments accepted in a rat Vogel drinking conflict paradigm over 3 min, as did the benzodiazepine anxiolytics, chlordiazepoxide (2.5–10 mg/kg p.o. 1 h pre-test) and alprazolam (0.2–5 mg/kg p.o. 1 h pre-test), but not the 5-HT_2C/2B receptor agonist, m-chlorophenylpiperazine (mCPP, 0.3–3 mg/kg i.p) or the 5-HT_1A receptor agonist, buspirone (5–20 mg/kg p.o. 1 h pre-test). The effect of BW 723C86 was unlikely to be secondary to enhanced thirst, as BW 723C86 did not increase the time that rats with free access to water spent drinking, nor did it reduce sensitivity to shock in the apparatus. The anti-punishment effect of BW 723C86 was opposed by prior treatment with the 5-HT_2C/2B receptor antagonist, SB-206553 (10 and 20 mg/kg p.o. 1 h pre-test), and the selective 5-HT_2B receptor antagonist, SB-215505 (1 and 3 mg/kg p.o. 1 h pre-test), but not by the selective 5-HT_2C receptor antagonist, SB-242084 (5 mg/kg p.o.), or the 5-HT_1A receptor antagonist, WAY 100635 (0.1 or 0.3 mg/kg s.c. 30 min pre-test). Thus, the anti-punishment action of BW 723C86 is likely to be 5-HT_2B receptor mediated. This is consistent with previous reports that BW 723C86 exhibited anxiolytic-like properties in both the social interaction and Geller-Seifter conflict tests.

Section snippets

Intorduction

The 5-HT₂ receptor family is thought to consist of three members, 5-HT_2A, 5-HT_2B and 5-HT_2C, on the basis of their similar structure and pharmacology and their supposed common coupling to the phosphatidyl inositol hydrolysis secondary messenger system, although this has never been demonstrated for the 5-HT_2B receptor in a physiological system (Baxter et al., 1995). The 5-HT_2B receptor was cloned from the rat stomach fundus (Foquet et al., 1992, Kursar et al., 1992) and is the most recent

Animals

Male Sprague Dawley (CD) rats (220–250 g) were housed in groups of six under a 12 h light/dark cycle (lights on 07.00 h) with free access to food (CRMX, special Diet Services) and water.

Vogel conflict test

Rats were water deprived for 20 h on day 1, prior to being placed in a uniformly lit operant conditioning chamber (45×25×25 cm) with a metal barred floor, into which a water bottle spout protruded. Rats were allowed to explore the chamber freely and drink for 3 min, timed from the first lick of the spout which

Effect of BW 723C86 and chlordiazepoxide on rat behaviour in a Vogel conflict test

BW 723C86 increased the number of punishments accepted in the rat Vogel conflict test over 3 min, as did chlordiazepoxide (F(6, 131)=13.5, P<0.01). The effect of BW 723C86 reached significance at 10 and 30 mg/kg i.p. and was numerically greater than the effect of chlordiazepoxide at the dose used (5 mg/kg i.p.) (Fig. 1). Neither BW 723C86 nor chlordiazepoxide significantly altered latency to drink in the test, but both treatments caused a numerical reduction in latency (mean±S.E.M. latency;

Discussion

BW 723C86 dose-dependently increased the number of punishments accepted in a rat Vogel conflict test. This effect was unlikely to be secondary to increased thirst, as BW 723C86 had no significant effect on drinking in the apparatus, nor has it previously been observed to increase drinking behaviour in rats with free access to water after either systemic or ICV administration (Kennett et al., 1997a). Furthermore, there was no evidence that BW 723C86 acted by reducing sensitivity to shock in the

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Anxiolytic-like actions of BW 723C86 in the rat Vogel conflict test are 5-HT2B receptor mediated

Abstract

Section snippets

Intorduction

Animals

Vogel conflict test

Effect of BW 723C86 and chlordiazepoxide on rat behaviour in a Vogel conflict test

Discussion

Trends in Pharmacological Science

FEBS Letters

Neuroscience

Neuropharmacology

Pharmacology and Therapeutics

Neuropharmacology

Neuropharmacology

FEBS Letters

Molecular Brain Research

FEBS Letters

Physiology and Behavior

Physiology and Behaviour

Involvement of 5-HT1B receptors in the anticonflict effect of mCPP in rats

Journal of Neural Transmission

5-HT and mechanisms of defence

Journal of Psychopharmacology

Anxiolytic-like actions of BW 723C86 in the rat Vogel conflict test are 5-HT_2B receptor mediated

Involvement of 5-HT_1B receptors in the anticonflict effect of mCPP in rats