P-CHLOROAMPHETAMINE-INDUCED AND D-FENFLURAMINE-INDUCED BRAIN-SEROTONIN RELEASE IN EXPERIMENTAL PORTAL-SYSTEMIC ENCEPHALOPATHY

Portal-systemic encephalopathy (PSE) is associated with increased brai n turnover of serotonin (5-HT) in vivo but the brain 5-HT output seems to be unaltered. Recent results suggest, however, that an augmented n eocortical 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 p ortacaval shunted (PCS) rats and sham-operated controls following loca l administration of p-chloroamphetamine (pCA) and d-fenfluramine (dFEN ), two specific 5-HT releasing agents. The basal neocortical extracell ular 5-HT concentrations were unaltered and the 5-HIAA levels were ele vated in experimental PSE, supporting an unchanged brain 5-HT output d espite elevated brain 5-HT metabolism. Perfusion with pCA or dFEN (5 m u M; 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 administratio n 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 obse rved between the two experimental groups following pCA perfusion (sham , 1100% versus PCS, 1470%). These results support our previous content ion of an enhanced neocortical 5-HT output in experimental chronic PSE under certain pharmacological conditions.