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Paradoxical decrease of brain 5-HT turnover by metergoline, a central 5-HT receptor blocker

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Summary

Since metergoline (1-methyl-8-beta-carbobenzyloxy-aminomethyl-10-alpha-ergoline) is a potent 5-HT antagonist in peripheral organs, its possible blocking effects on 5-HT receptors in the rat brain were investigated. In vitro, metergoline inhibited both the specific high affinity binding of 3H-5-HT onto synaptosomal membranes (IC 50=18 nM) and the stimulating effect of 10 μM 5-HT on the adenylate cyclase activity in colliculi homogenates from newborn rats (IC 50=12 μM). In vivo, the administration of metergoline (10 mg/kg i.p., 60 min before death) resulted in a significant decrease in the 3H-5-HT binding capacity of synaptosomal membranes from the forebrain of adult rats. Taken together, these data clearly indicated that metergoline is a potent blocker of some serotoninergic receptors in the rat brain. Surprisingly, the changes in 5-HT turnover occurring in the brainstem and in the forebrain 1 h after metergoline (2–10 mg/kg) treatment were similar to those normally induced by a central 5-HT agonist: both the rate of 5-HT utilisation and that of 5-HT synthesis were significantly decreased. These changes were in contrast to the acceleration of 5-HT turnover induced by the administration of another potent central 5-HT antagonist, methiothepin. These results are discussed in relation to the possible existence of several types of serotoninergic receptors in the rat brain. It is possible that the positive feedback regulation of 5-HT turnover is triggered by the blockade of serotoninergic receptors sensitive to methiothepin, but not to metergoline.

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Authors and Affiliations

  1. Groupe NB, INSERM U 114, 11, place Marcelin Berthelot, F-75231, Paris Cedex 5, France

    S. Bourgoin, F. Artaud, F. Héry, J. Glowinski & M. Hamon

  2. Laboratoire de Physiologie Cellulaire, Collège de France, 11, place Marcelin Berthelot, F-75231, Paris Cedex 5, France

    J. Bockaert

Authors
  1. S. Bourgoin
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  2. F. Artaud
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  3. J. Bockaert
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  4. F. Héry
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  5. J. Glowinski
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  6. M. Hamon
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Bourgoin, S., Artaud, F., Bockaert, J. et al. Paradoxical decrease of brain 5-HT turnover by metergoline, a central 5-HT receptor blocker. Naunyn-Schmiedeberg's Arch. Pharmacol. 302, 313–321 (1978). https://doi.org/10.1007/BF00508301

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  • DOI: https://doi.org/10.1007/BF00508301

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