Effects of the 5‐HT<sub>2B</sub> receptor agonist, BW 723C86, on three rat models of anxiety

Kennett, Guy A.; Bright, Fiona; Trail, Brenda; Baxter, G.S.; Blackburn, T.P.

doi:10.1111/j.1476-5381.1996.tb15304.x

Cited by 106 publications

(53 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…According with the results previously obtained by Cheng and Shibata [17] in the hindquarters of old SHR, our experiments showed a higher increased responsiveness for the highest doses tested compared with the vasoconstrictions induced by the same doses in Wistar rats [13]. The absence of vasoconstrictor activity due to the new selective 5-HT 2B agonist BW 723C86 (pE 50 value 7.9) [28], at all the doses used together with the vasoconstriction produced by intra-arterial administration of the 5-HT 2C receptor agonist m-CPP (pE 50 values of 7.4 and 6.9 for 5-HT 2B and 5-HT 2C receptors, respectively [27]), allow us to rule out the possible participation of 5-HT 2B receptors in the vasoconstrictor action. These results are in accordance with the recognized endothelial localization of this receptor subtype, and the vasorelaxation but not vasoconstriction mediated via nitric oxide release [30].…”

Section: Discussionsupporting

confidence: 72%

Vasoconstrictor Responses to 5-Hydroxytryptamine in the Autoperfused Hindquarters of Spontaneously Hypertensive Rats

Calama

Morán²,

Urbina³

et al. 2004

Pharmacology

View full text Add to dashboard Cite

In this work we studied the responses and receptors involved in the effects of intra-arterial 5-hydroxytryptamine (5-HT) in the in situ autoperfused hindquarters of spontaneously hypertensive rats (SHR). Intra-arterial administration of the highest doses (50–1,000 ng/kg) produced a vasoconstrictor effect that was inhibited by ritanserin (a selective 5-HT₂ receptor antagonist), SB 206553 (a selective 5-HT_2B/2C receptor antagonist) and spiperone (a nonspecific 5-HT_1/2A receptor antagonist), and was mimicked by α-methyl-5-HT (a selective 5-HT₂ receptor agonist) and m-CPP (a selective 5-HT_2C receptor agonist), but not by the intra-arterial administration of BW 723C86, a selective 5HT_2B receptor agonist. SB 206553 and spiperone inhibited α-methyl-5HT-induced vasoconstriction in the hindquarters of SHR. Our data suggest that the vasoconstrictor response induced by 5-HT in the autoperfused hindquarters of SHR is mainly mediated by the activation of 5-HT_2A and 5-HT_2C receptors.

show abstract

Section: Discussionsupporting

confidence: 72%

Vasoconstrictor Responses to 5-Hydroxytryptamine in the Autoperfused Hindquarters of Spontaneously Hypertensive Rats

Calama

Morán²,

Urbina³

et al. 2004

Pharmacology

View full text Add to dashboard Cite

show abstract

“…However, the 5-HT 2B receptor is located principally in the periphery and only sparsely in the central nervous system in rats (Pompeiano et al, 1994). In addition, although it has been reported that a selective 5-HT 2B receptor agonist exhibited anxiolytic effects in rodents, a selective 5-HT 2B receptor antagonist was without effect (Kennett et al, 1996(Kennett et al, , 1998. Last, anxiolytic activity of a mixed 5-HT 2C/2B receptor antagonist has been ascribed to activity at the 5-HT 2C but not 5-HT 2B receptor (Bromidge et al, 2000).…”

Section: Discussionmentioning

confidence: 80%

Anxiolytic- and Antidepressant-Like Profile of ATC0065 and ATC0175: Nonpeptidic and Orally Active Melanin-Concentrating Hormone Receptor 1 Antagonists

Chaki¹,

Funakoshi²,

Hirota-Okuno³

et al. 2005

J Pharmacol Exp Ther

125

View full text Add to dashboard Cite

Melanin-concentrating hormone (MCH) is a cyclic peptide produced in the lateral hypothalamus. It has been implicated in a number of physiological processes including feeding behavior, energy balance, and the regulation of emotional states. (1-10 mg/kg) significantly reduced immobility time in the forced swimming test in rats, indicating antidepressantlike effects. Both ATC0065 and ATC0175 significantly reversed swim stress-induced anxiety in the elevated plus-maze test in rats and stress-induced hyperthermia in mice. ATC0175 significantly increased social interaction between unfamiliar rats and reduced separation-induced vocalizations in guinea pig pups, indicating anxiolytic potential. In contrast, ATC0065 and ATC0175 did not affect spontaneous locomotor activity or rotarod performance in rats. These findings indicate that ATC0065 and ATC0175 are potent and orally active MCHR1 antagonists with anxiolytic and antidepressant activity in rodents.Melanin-concentrating hormone (MCH) is a cyclic neuropeptide originally isolated from salmon pituitary (Kawaguchi et al., 1983). In mammals, MCH is produced predominantly by neurons in the lateral hypothalamus and zona incerta with extensive projections throughout the brain (Bittencourt et al., 1992). This expression pattern supports a role for MCH in numerous physiological processes including motivated behavior, stress responses, regulation of neuroendocrine function, and feeding.Several groups independently identified a G protein-coupled receptor, SLC-1/GPR24, as an MCH receptor (MCHR1) (Bachner et al., 1999;Chambers et al., 1999;Lembo et al., 1999;Saito et al., 1999;Shimomura et al., 1999), and MCHR2 was identified subsequently on the basis of the sequence homology to MCHR1 Hill et al., 2001;Mori et al., 2001;Sailer et al., 2001). Potential physiological functions of MCHR2 have not been elucidated due to the species-specific expression of the receptor (Tan et al., 2002); therefore, current research has focused on MCHR1.There are several lines of evidence implicating MCHR1 in feeding and energy homeostasis. MCHR1 mRNA is increased Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

show abstract

“…Moreover, the selective 5-HT 2B receptor antagonist, SB204,741 (Cussac et al 2002), showed no substitution to mirtazapine at doses active in other behavioral procedures like modulation of sleep architecture (Kantor et al 2004). In addition, though 5-HT 2B receptor blockade reduces the locomotor actions of 3,4-methylenedioxymethamphetamine (ecstasy; MDMA; Doly et al 2008), and 5-HT 2B receptor stimulation is associated with anxiolytic properties (Kennett et al 1996), there is no evidence that antagonism of central 5-HT 2B receptors greatly affects mood. A role of 5-HT 2A receptor blockade in the DS properties of mirtazapine also appears unlikely inasmuch as SB242,084, SB243,213, and S32006 all possess low affinity for 5-HT 2A receptors, and the highly selective antagonist at 5-HT 2A receptors, MDL100,907 and SR46349-B, failed to significantly substitute for mirtazapine.…”

Section: Discussionmentioning

confidence: 99%

Discriminative stimulus properties of the “atypical” antidepressant, mirtazapine, in rats: a pharmacological characterization

Dekeyne

Millan

2008

Psychopharmacology

View full text Add to dashboard Cite

Rationale Though interoceptive properties of antidepressants have been described, discriminative stimulus (DS) properties of mirtazapine, which does not affect monoamine reuptake, remain uncharacterized. Objectives The objectives of the study are to train rats to recognize a mirtazapine DS, then perform substitution studies with other antidepressants and drugs acting at sites occupied by mirtazapine. Materials and methods Using a two-lever, fixed-ratio 10 schedule, rats were trained to discriminate mirtazapine (2.5 mg/kg, i.p.) from saline. Results Sessions, 63± 8, were necessary to reach the criterion for 14 rats that all subsequently recognized (100%) mirtazapine at the training dose. Mirtazapine blocks serotonin (5-HT) 2C receptors, and the 5-HT 2C antagonists, SB242,084, SB243,213 and S32006, revealed dosedependent and full (≥80%) substitution at doses of 2.5, 2.5, and 0.63 mg/kg, respectively. By contrast, the 5-HT 2A antagonists, MDL100,907 and SR46349-B, the 5-HT 2B antagonist, SB204,741, and the 5-HT 3 antagonist, ondansetron, showed no significant substitution. Though mirtazapine indirectly recruits 5-HT 1A receptors, the 5-HT 1A agonists, buspirone and 8-OH-DPAT, did not substitute. Mirtazapine blocks α 2 -adrenoceptors, but several α 2 -adrenoceptor antagonists (yohimbine, RX821,002 and atipamezole) failed to substitute. Despite blockade by mirtazapine of histamine H 1 receptors, no substitution was seen with the selective H 1 antagonist, pyrilamine. Finally, the selective noradrenaline reuptake inhibitor, reboxetine (0.16), fully substituted for mirtazapine, whereas the 5-HT/noradrenaline reuptake inhibitors, duloxetine and S33005, several 5-HT reuptake inhibitors (citalopram, fluvoxamine, and paroxetine) and the dopamine reuptake inhibitors, bupropion and GBR12,935, did not substitute. Conclusion Mirtazapine elicits a DS in rats for which selective antagonists at 5-HT 2C receptors display dosedependent substitution, whereas drugs acting at other sites recognized by mirtazapine are ineffective.

show abstract

Effects of the 5‐HT_2B receptor agonist, BW 723C86, on three rat models of anxiety

Cited by 106 publications

References 26 publications

Vasoconstrictor Responses to 5-Hydroxytryptamine in the Autoperfused Hindquarters of Spontaneously Hypertensive Rats

Vasoconstrictor Responses to 5-Hydroxytryptamine in the Autoperfused Hindquarters of Spontaneously Hypertensive Rats

Anxiolytic- and Antidepressant-Like Profile of ATC0065 and ATC0175: Nonpeptidic and Orally Active Melanin-Concentrating Hormone Receptor 1 Antagonists

Discriminative stimulus properties of the “atypical” antidepressant, mirtazapine, in rats: a pharmacological characterization

Contact Info

Product

Resources

About

Effects of the 5‐HT2B receptor agonist, BW 723C86, on three rat models of anxiety

Cited by 106 publications

References 26 publications

Vasoconstrictor Responses to 5-Hydroxytryptamine in the Autoperfused Hindquarters of Spontaneously Hypertensive Rats

Vasoconstrictor Responses to 5-Hydroxytryptamine in the Autoperfused Hindquarters of Spontaneously Hypertensive Rats

Anxiolytic- and Antidepressant-Like Profile of ATC0065 and ATC0175: Nonpeptidic and Orally Active Melanin-Concentrating Hormone Receptor 1 Antagonists

Discriminative stimulus properties of the “atypical” antidepressant, mirtazapine, in rats: a pharmacological characterization

Contact Info

Product

Resources

About

Effects of the 5‐HT_2B receptor agonist, BW 723C86, on three rat models of anxiety