Endogenous noradrenaline as modulator of hippocampal serotonin (5-HT)-release

Dual effects of yohimbine, rauwolscine and corynanthine as α-adrenoceptor antagonists and 5-HT-receptor agonists
  • Thomas J. Feuerstein
  • Georg Hertting
  • Rolf Jackisch
Article

Summary

The modulation of hippocampal serotonin (5-HT)-release by noradrenaline was studied in rabbit hippocampal slices, which were preincubated with 3H-serotonin and then superfused continuously. Electrical field stimulation of the slices elicited a tritium overflow, which was decreased by clonidine in a concentration dependent manner. Phentolamine antagonized the effects of clonidine and, given alone, increased the evoked tritium overflow. This facilitatory effect of phentolamine was further enhanced in the presence of (+)oxaprotilin, a highly selective noradrenaline uptake inhibitor, whereas the (-)enantiomer of oxaprotilin, which does not affect noradrenaline uptake, was inactive. (+)Oxaprotilin but not (-)oxaprotilin, given alone, inhibited the evoked tritium overflow. The inhibitory effect of (+)oxaprotilin was antagonized by phentolamine.

In the presence of phentolamine, the α-adrenoceptor antagonists yohimbine, rauwolscine and corynanthine decreased the evoked 5-HT-release concentration dependently. Their inhibitory effects were, however, abolished (corynanthine) or inversed to a facilitation of release (yohimbine, rauwolscine) if instead of phentolamine the 5-HT-receptor antagonist metitepin was present. Therefore we suggest that yohimbine, rauwolscine and corynanthine, in addition to their α-adrenoceptor antagonistic properties, may act as agonists at 5-HT-autoreceptors. Possibly the indol part of their molecules is responsible for this effect. Furthermore, our results provide evidence for the modulation of hippocampal 5-HT-release by endogenous noradrenaline.

Key words

Serotonin release Hippocampus α2-Adrenoceptors Yohimbine Rauwolscine Oxaprotilin 

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Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • Thomas J. Feuerstein
    • 1
  • Georg Hertting
    • 1
  • Rolf Jackisch
    • 1
  1. 1.Pharmakologisches InstitutUniversität FreiburgFreiburg i. Br.Federal Republic of Germany

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