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p-chloroamphetamine- and d-fenfluramine-induced brain serotonin release in experimental portal-systemic encephalopathy

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Abstract

Portal-systemic encephalopathy (PSE) is associated with increased brain turnover of serotonin (5-HT)in vivo but the brain 5-HT output seems to be unaltered. Recent results suggest, however, that an augmented neocortical 5-HT release in experimental chronic PSE may prevail under certain conditions. In the present study, neocortical extracellular 5-HT and 5-hydroxyindoleacetic-3-acid (5-HIAA) levels were measured in portacaval shunted (PCS) rats and sham-operated controls following local administration of p-chloroamphetamine (pCA) and d-fenfluramine (dFEN), two specific 5-HT releasing agents. The basal neocortical extracellular 5-HT concentrations were unaltered and the 5-HIAA levels were elevated in experimental PSE, supporting an unchanged brain 5-HT output despite elevated brain 5-HT metabolism. Perfusion with pCA or dFEN (5 μM; one 20-min pulse) produced marked increases in brain 5-HT release both in PCS and sham-operated rats compared with corresponding basal values. While no difference in the 5-HT response to dFEN administration was seen between sham (5-HT levels increased by 330%) and PCS (500%) rats, a clear difference (P<0.05) in the brain 5-HT output was observed between the two experimental groups following pCA perfusion (sham, 1100% versus PCS, 1470%). These results support our previous contention of an enhanced neocortical 5-HT output in experimental chronic PSE under certain pharmacological conditions.

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Authors and Affiliations

  1. Department of Clinical Pharmacology, Institute of Laboratory Medicine, Lund University Hospital, S-221 85, Lund, Sweden

    Peter B. F. Bergqvist, Cecilia Wikell, Gustav Apelqvist & Finn Bengtsson

  2. Department Pharmacology, University of Gothenburg, Gothenburg, Sweden

    Stephan Hjorth

Authors
  1. Peter B. F. Bergqvist
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  2. Stephan Hjorth
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  3. Cecilia Wikell
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  4. Gustav Apelqvist
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  5. Finn Bengtsson
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Correspondence to Peter B. F. Bergqvist.

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Bergqvist, P.B.F., Hjorth, S., Wikell, C. et al. p-chloroamphetamine- and d-fenfluramine-induced brain serotonin release in experimental portal-systemic encephalopathy. Metab Brain Dis 12, 229–236 (1997). https://doi.org/10.1007/BF02674615

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