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. 1994 Oct;113(2):425–430. doi: 10.1111/j.1476-5381.1994.tb17006.x

Effect of acute administration of the 5-HT1A receptor ligand, lesopitron, on rat cortical 5-HT and dopamine turnover.

M Ballarín 1, A Carceller 1, X Guitart 1
PMCID: PMC1510099  PMID: 7530571

Abstract

1. The involvement of presynaptic 5-hydroxytryptamine1A (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 behavior in rats (30 micrograms 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 micrograms 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.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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