The role of 5-HT1B/1D receptors in the modulation of 5-hydroxytryptamine levels in the frontal cortex of the conscious guinea pig

Roberts, Claire; Price, Gary; Jones, Brian

doi:10.1016/s0014-2999(97)00156-8

Cited by 47 publications

(18 citation statements)

References 29 publications

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“…Specifically, regional and interspecies differences between dorsal and median raphe innervated brain regions within both the guinea pig and rat have been studied. These results confirm that 5-HT 1B autoreceptors control in vivo 5-HT release in terminal regions of the guinea pig brain (Roberts et al 1997). Extracellular 5-HT in the dentate gyrus was increased following acute administration of SB-224289, therefore indicating that 5-HT 1B autoreceptors limit baseline 5-HT release in the guinea pig dentate gyrus.…”

Section: Discussionsupporting

confidence: 77%

“…Administration of compounds with 5-HT 1B receptor agonist activity such as sumatriptan or RU 24969 (nonselective 5-HT 1B/1D receptor agonists) either via the microdialysis probe (Roberts et al 1997) or systemically (Martin et al 1992) have been shown to cause a decrease in brain extracellular 5-HT in rats and guinea pigs in vivo. This decrease can be reversed by selective (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Differential autoreceptor control of extracellular 5-HT in guinea pig and rat: species and regional differences

Hughes

Dawson

2004

Psychopharmacology

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These data indicate that there is a species difference in the autoreceptor control of 5-HT release. Furthermore, in the guinea pig there is a divergence between dorsal and median raphe innervated brain regions. On the basis that antagonism of 5-HT(1A) and 5-HT(1B) receptors produced an immediate increase in extracellular 5-HT in multiple brain regions in the guinea pig, it is suggested that this might be a novel mechanism for achieving antidepressant efficacy.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Differential autoreceptor control of extracellular 5-HT in guinea pig and rat: species and regional differences

Hughes

Dawson

2004

Psychopharmacology

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“…Therefore, the lack of effect of 5-HT 1B receptor antagonists in the frontal cortex in an intact animal may indicate that either there is little tone at terminal 5-HT autoreceptors in vivo in this brain region, or that drug effects at the terminal are being compromised by simultaneous effects at the cell body level. We have previously reported that perfusion of less selective 5-HT 1B/1D receptor antagonists, down the dialysis probe, into the frontal cortex increased extracellular 5-HT levels in the guinea-pig (Roberts et al 1997). This suggests that there is 5-HT tone at the terminal autoreceptors innervated from the DRN, and the lack of effect of SB-236057-A in the frontal cortex may be a result of additional receptor blockade in the DRN.…”

Section: Discussionmentioning

confidence: 97%

The effect of SB-236057-A, a selective 5-HT 1B receptor inverse agonist, on in vivo extracellular 5-HT levels in the freely-moving guinea-pig

Roberts

Hatcher

Hagan

et al. 2000

Naunyn-Schmiedeberg's Archives of Pharmacology

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5-HT1B autoreceptors are involved in the control of extracellular 5-HT levels from both the terminal and cell body regions of serotonergic neurones. In this study we report on the effect of a selective and potent 5-HT1B receptor inverse agonist, SB-236057-A (1'-ethyl-5-(2'-methyl-4'-(5-methyl- 1,3,4-oxadiazolyl-2-yl)biphenyl-4-carbonyl)-2,3,6,7-tetrahydros piro [furo[2,3-f]indole-3,4' -piperidine] hydrochloride), on extracellular 5-HT levels in the cortex and dentate gyrus of the freely-moving guinea-pig, using the technique of in vivo microdialysis. SB-236057-A had ca. 23% bioavailability following oral drug administration. In vivo hypothermia pharmacodynamic assays demonstrated it was brain penetrant with a duration of action in excess of 18 h. SB-236057-A (0.75 mg/kg p.o.) increased extracellular 5-HT levels in the dentate gyrus to a maximum of 167+/-7% of basal but had no effect in the frontal cortex. However, a small increase in cortical 5-HT levels (117+11% of basal) was evident at 2.5 mg/kg p.o. In addition, SB-236057-A (0.75 mg/kg and 2.5 mg/kg p.o.) antagonised the sumatriptan-induced inhibition of extracellular 5-HT levels in the guinea-pig frontal cortex. These differences were attributed to MRN-innervated regions (e.g. dentate gyrus) being more responsive to 5-HT1B receptor-mediated negative feedback than DRN-innervated regions (e.g. frontal cortex). In the dentate gyrus, the increase in 5-HT release induced by SB-236057-A (0.75 mg/kg p.o.) was comparable to that after 14 days of paroxetine (10 mg/kg p.o.) administration, reaching a maximum of 183+/-13% of basal. These data suggest that acute 5-HT1B receptor blockade, by virtue of increased 5-HT release in the dentate gyrus, may provide a rapidly acting antidepressant.

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“…Blockade of 5-HT 1B receptors alone has been shown to acutely increase levels of serotonin in the guinea pig frontal cortex and hippocampus as well as augment the effects of SSRIs on serotonin levels. 45 Combining the selective 5-HT 1A antagonist, WAY-100635, with the 5-HT 1B receptor antagonist, SB-224289, produced marked elevations in serotonin levels in the guinea pig. 46 These latter results curiously suggest that combining 5-HT 1A and 5-HT 1B receptor antagonism can elevate serotonin and, consequently, potentially be an effective strategy to treat depression.…”

Section: Additional Multitarget Monoamine Strategiesmentioning

confidence: 99%

Innovative approaches for the development of antidepressant drugs: Current and future strategies

Schechter¹,

Ring²,

Beyer³

et al. 2005

Neurotherapeutics

183

100

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Summary: Depression is a highly debilitating disorder that has been estimated to affect up to 21% of the world population. Despite the advances in the treatment of depression with selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), there continue to be many unmet clinical needs with respect to both efficacy and side effects. These needs range from efficacy in treatment resistant patients, to improved onset, to reductions in side effects such as emesis or sexual dysfunction. To address these needs, there are numerous combination therapies and novel targets that have been identified that may demonstrate improvements in one or more areas. There is tremendous diversity in the types of targets and approaches being taken. At one end of a spectrum is combination therapies that maintain the benefits associated with SSRIs but attempt to either improve efficacy or reduce side effects by adding additional mechanisms (5-HT 1A , 5-HT 1B , 5-HT 1D , 5-HT 2C , ␣-2A). At the other end of the spectrum are more novel targets, such as neurotrophins (BDNF, IGF), based on recent findings that antidepressants induce neurogenesis. In between, there are many approaches that range from directly targeting serotonin receptors (5-HT 2C , 5-HT 6 ) to targeting the multiplicity of potential mechanisms associated with excitatory (glutamate, NMDA, mGluR2, mGluR5) or inhibitory amino acid systems (GABA) or peptidergic systems (neurokinin 1, corticotropin-releasing factor 1, melanin-concentrating hormone 1, V1b). The present review addresses the most exciting approaches and reviews the localization, neurochemical and behavioral data that provide the supporting rationale for each of these targets or target combinations.

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The role of 5-HT1B/1D receptors in the modulation of 5-hydroxytryptamine levels in the frontal cortex of the conscious guinea pig

Cited by 47 publications

References 29 publications

Differential autoreceptor control of extracellular 5-HT in guinea pig and rat: species and regional differences

Differential autoreceptor control of extracellular 5-HT in guinea pig and rat: species and regional differences

The effect of SB-236057-A, a selective 5-HT 1B receptor inverse agonist, on in vivo extracellular 5-HT levels in the freely-moving guinea-pig

Innovative approaches for the development of antidepressant drugs: Current and future strategies

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