European Journal of Pain SupplementsVolume 5, Issue S1 p. 181-181 F643 SPINAL AND SUPRASPINAL ACTION OF THE NEW SELECTIVE SIGMA-1 RECEPTOR ANTAGONIST (S1RA) ON PAIN MODELS A. Vidal, A. Vidal Department of Pharmacology, ESTEVE, Barcelona, SpainSearch for more papers by this authorB. Fernández, B. Fernández Department of Pharmacology, ESTEVE, Barcelona, SpainSearch for more papers by this authorA. Carceller, A. Carceller Department of Pharmacology, ESTEVE, Barcelona, SpainSearch for more papers by this authorL. Romero, L. Romero Department of Pharmacology, ESTEVE, Barcelona, SpainSearch for more papers by this authorJ.M. Vela, J.M. Vela Department of Pharmacology, ESTEVE, Barcelona, SpainSearch for more papers by this authorD. Zamanillo, D. Zamanillo Department of Pharmacology, ESTEVE, Barcelona, SpainSearch for more papers by this author A. Vidal, A. Vidal Department of Pharmacology, ESTEVE, Barcelona, SpainSearch for more papers by this authorB. Fernández, B. Fernández Department of Pharmacology, ESTEVE, Barcelona, SpainSearch for more papers by this authorA. Carceller, A. Carceller Department of Pharmacology, ESTEVE, Barcelona, SpainSearch for more papers by this authorL. Romero, L. Romero Department of Pharmacology, ESTEVE, Barcelona, SpainSearch for more papers by this authorJ.M. Vela, J.M. Vela Department of Pharmacology, ESTEVE, Barcelona, SpainSearch for more papers by this authorD. Zamanillo, D. Zamanillo Department of Pharmacology, ESTEVE, Barcelona, SpainSearch for more papers by this author First published: 30 January 2012 https://doi.org/10.1016/S1754-3207(11)70623-XRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume5, IssueS1September 2011Pages 181-181 RelatedInformation

European Journal of PainVolume 13, Issue S1 p. S94-S94 304 NEUROCHEMICAL CHARACTERIZATION OF THE FORMALIN TEST USING IN VIVO MICRODIALYSIS IN THE IPSILATERAL SPINAL DORSAL HORN IN AWAKE RATS B. Fernández-Pastor, B. Fernández-Pastor Department of Pharmacology, Laboratorios ESTEVE, Barcelona, SpainSearch for more papers by this authorA. Carceller, A. Carceller Department of Pharmacology, Laboratorios ESTEVE, Barcelona, SpainSearch for more papers by this authorD. Zamanillo, D. Zamanillo Department of Pharmacology, Laboratorios ESTEVE, Barcelona, SpainSearch for more papers by this authorJ.M. Vela, J.M. Vela Department of Pharmacology, Laboratorios ESTEVE, Barcelona, SpainSearch for more papers by this author B. Fernández-Pastor, B. Fernández-Pastor Department of Pharmacology, Laboratorios ESTEVE, Barcelona, SpainSearch for more papers by this authorA. Carceller, A. Carceller Department of Pharmacology, Laboratorios ESTEVE, Barcelona, SpainSearch for more papers by this authorD. Zamanillo, D. Zamanillo Department of Pharmacology, Laboratorios ESTEVE, Barcelona, SpainSearch for more papers by this authorJ.M. Vela, J.M. Vela Department of Pharmacology, Laboratorios ESTEVE, Barcelona, SpainSearch for more papers by this author First published: 12 January 2012 https://doi.org/10.1016/S1090-3801(09)60307-4Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume13, IssueS1September 2009Pages S94-S94 RelatedInformation

1 The involvement of presynaptic 5-hydroxytryptamine(1A) (5-HT1A) autoreceptors in the anxiolytic-like properties of lesopitron (E-4424) (2-{4-[4-(4-chloro-1-pyrazolyl)butyl]-1-piperazinyl}pyrimidine) was studied. Brain microdialysis was used to examine the effect of the drug on the release of 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the frontal cortex of awake, freely moving rats. Moreover, extracellular cortical 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were also studied to assess the possible participation of dopaminergic systems.2 Lesopitron administered at a dose which induces anxiolytic behaviour in rats (30 mu g kg(-1), i.p.) markedly reduced 5-HT levels (to 45% of the basal value) in cortical perfusates, having no effect on 5-HIAA, DOPAC and HVA. The effects of lesopitron were compared with those produced by the anxiolytic, and structurally related compound, buspirone.3 Buspirone administered at a dose inducing anxiolytic-like effects in rats (5 mg kg(-1), i.p.) produced a marked decrease in cortical 5-HT levels (to 20% of the basal value), but in contrast to lesopitron, buspirone produced a pronounced increase in cortical DOPAC (to 300% of the basal value) and HVA (to 400% of the basal value) levels. Buspirone administered at a low dose (30 mu g kg(-1), i.p.) was unable to affect cortical 5-HT levels.4 To test the hypothesis that the 5-HT decreasing effect of lesopitron could be due to 5-HT1A autoreceptor (somatodendritic)-mediated inhibition of 5-HT neurotransmission, lesopitron was administered locally into the raphe nuclei. Intraraphe administration of 10 mu M lesopitron caused a decrease in cortical 5-HT levels (the effect being of the same order as that obtained after systemic injection), with no effect on 5-HIAA, DOPAC and HVA. Raphe 5-HT extracellular levels were not modified after intraraphe administration of lesopitron, indicating the absence of 5-HT reuptake blocking properties.5 We concluded that lesopitron, at an anxiolytic dose produced a marked inhibition of 5-HT release in the frontal cortex of awake, freely moving rats. This effect was observed after systemic administration as well as after intraraphe administration of the drug, suggesting an agonistic action at raphe 5-HT1A autoreceptors controlling 5-HT release in the projecting areas. In contrast to buspirone, lesopitron treatment had no effect on cortical DOPAC or HVA levels.

The characteristics of the serotonin (5-HT) output in the dorsal and median raphe nuclei of the rat were studied using in vivo microdialysis. The basal output of 5-HT increased after KCl was added to the perfusion fluid. In contrast, neither the omission of calcium ions nor the addition of 0.5 muM tetrodotoxin affected dialysate 5-HT or 5-hydroxyindoleacetic acid (5-HIAA). Reserpine did not decrease the output of 5-HT and 5-HIAA 24 h later and p-chloroamphetamine increased 5-HT in both vehicle- and reserpine-treated rats severalfold. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), at 1 or 10 muM, perfused into the raphe did not change the outputs of 5-HT or 5-HIAA. Higher doses (0. 1, 1, and 10 mM) increased extracellular 5-HT in the raphe, probably via an inhibition of uptake. In animals bearing two probes (raphe nuclei and ventral hippocampus), only the 10 mM dose of 8-OH-DPAT perfused into the raphe decreased the hippocampal output of 5-HT and 5-HIAA. The systemic injection of 0.1 mg/kg 8-OH-DPAT decreased dialysate 5-HT and 5-HIAA in the raphe and hippocampus. These results suggest that extracellular 5-HT in raphe nuclei originates from a cytoplasmic pool and is not dependent on either nerve impulse of 5-HT neurons or local activation of 5-HT1A receptors.

The extracellular concentrations of 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) have been determined in six brain areas of awake rats (frontal cortex, striatum, hypothalamus, hippocampus, inferior colliculus, and raphe nuclei) using intracerebral microdialysis. The extracellular levels of 5-HT showed no significant differences among the brain regions studied. The tissue levels of 5-HT and 5-HIAA as well as the extracellular concentration of 5-HIAA were significantly higher in raphe nuclei. The regional distribution of tissue and extracellular 5-HIAA were very similar, suggesting that extracellular 5-HIAA depends mainly on the output from the intracellular compartment. On the other hand, extracellular 5-HT and tissue 5-HT showed a different distribution pattern. The tissue/extracellular ratio for 5-HT ranged from 739 in frontal cortex to 2,882 in raphe, whereas it only amounted to 1.8-3.6 for 5-HIAA. The relationship between the present results and the density of 5-HT uptake sites in these areas is discussed.