p-Chloroamphetamine- and d-fenfluramine-induced brain serotonin release in experimental portal-systemic encephalopathy.
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 microM; 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.
Bergqvist
P B
PB
Department of Clinical Pharmacology, Institute of Laboratory Medicine, Lund University, Sweden. Peter.Bergqvist@klinfarm.lu.se
Hjorth
S
S
Wikell
C
C
Apelqvist
G
G
Bengtsson
F
F
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D005277:Fenfluramine / Q000494:pharmacology*; D006501:Hepatic Encephalopathy / Q000378:metabolism*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology*; D010133:p-Chloroamphetamine / Q000494:pharmacology*
D018490:Serotonin Agents; D005277:Fenfluramine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D010133:p-Chloroamphetamine