A 5-HT 7 heteroreceptor-mediated inhibition of [ 3H]serotonin release in raphe nuclei slices of the rat: Evidence for a serotonergic-glutamatergic interaction

Laszlo G. Harsing, Ibolya Prauda, Jozsef Barkoczy, Peter Matyus, Zsolt Juranyi

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Abstract

Midbrain slices containing the dorsal and medial raphe nuclei were prepared from rat brain, loaded with [ 3H]serotonin ([ 3H]5-HT), superfused, and the electrically induced efflux of radioactivity was determined. The nonselective 5-HT receptor agonist 5-carboxamido-tryptamine (5-CT; 0.001 to 1 μM) inhibited the electrically stimulated [ 3H]5-HT overflow from raphe nuclei slices (IC 50 of 3.34 ± 0.37 nM). This effect of 5-CT on [ 3H]5-HT overflow was antagonized by the 5-HT 7 receptor antagonist SB-258719 (10 μM) and the 5-HT 1B/1D antagonist SB-216641 (1 μM), the IC 50 values for 5-CT in the presence of SB-258719 and SB-216641 were 94.23 ± 4.84 and 47.81 ± 4.66 nM. The apparent pA 2 values for SB-258719 and SB-216641 against 5-CT were 6.43 and 7.12, respectively. The inhibitory effect of 5-CT on [ 3H]5-HT overflow was weakly antagonized by 10 μM of WAY-100635, a 5-HT 1A receptor antagonist (IC 50 6.65 ± 0.56 nM, apparent pA 2 4.99). The antagonist effect of SB-258719 (10 μM) on 5-CT-evoked [ 3H]5-HT overflow inhibition was also determined in the presence of 1 μM SB-216641 or 1 μM SB-216641 and 10 μM WAY-100635, and additive interactions were found between the antagonists of 5-HT 7 and 5-HT 1 receptor subtypes. Addition of the Na + channel blocker tetrodotoxin (1 μM) in the presence of SB-216641 (1 μM) and WAY-100635 (10 μM) attenuated the inhibitory effect of 5-CT on KCl-induced [ 3H]5-HT overflow. These findings indicate that 5-CT inhibits [ 3H]5-HT overflow from raphe nuclei slices of the rat by stimulation of 5-HT 7 and 5-HT 1B/1D receptors, whereas the role of 5-HT 1A receptors in this inhibition is less pronounced. They also suggest that 5-HT 7 receptors are probably not located on serotonergic neurons and thus may serve as heteroreceptors in regulation of 5-HT release in the raphe nuclei. 5-CT (0.1 μM) also inhibited [ 3H]glutamate release, and SB-258719 (10 μM) suspended this effect. We therefore speculated that the axon terminals of the glutamatergic cortico-raphe neurons may possess 5-HT 7 receptors that inhibit glutamate release, which consequently leads to decreased activity of serotonergic neurons. The postulated glutamatergic-serotonergic interaction in the raphe nuclei was further evidenced by the finding that N-methyl-d-aspartate and AMPA enhanced [ 3H]5-HT release.

Original languageEnglish
Pages (from-to)1487-1497
Number of pages11
JournalNeurochemical research
Volume29
Issue number8
DOIs
Publication statusPublished - Aug 1 2004

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Keywords

  • 5Carboxamidotryptamine
  • 5HT receptor
  • 5HT receptor
  • 5HT(1A) receptor
  • 5HT(1B1D) receptor
  • Hserotonin release
  • SB216641
  • SB258719
  • SB271046
  • WAY100635
  • raphe nuclei

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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