Modulation of hepatic encephalopathy in rats with thioacetamide-induced acute liver failure by serotonin antagonists.
OBJECTIVE
Accumulated neurochemical data in different animal models of fulminant hepatic failure and in humans with hepatic encephalopathy suggest that serotoninergic tone is increased in the brain in hepatic encephalopathy. Since neurochemical alterations may not have behavioural or electrophysiological consequences the contribution of the serotoninergic system to the pathogenesis of hepatic encephalopathy was explored.


METHODS
The effects of drugs modulating serotoninergic neurotransmission, the nonselective serotonin receptor antagonist methysergide and the serotonin2 receptor antagonist seganserin were tested neuropharmacologically in thioacetamide-induced acute liver failure in rats.


RESULTS
Methysergide had no effect in control rats, but dose dependently increased motor activity in stage II-III hepatic encephalopathy by 232% (5 mg/kg methysergide), 531% (10 mg/kg) and 507% (20 mg/kg). In contrast, seganserin had no effect in encephalopathic rats.


CONCLUSIONS
It is suggested that the beneficial effects of methysergide are serotonin, receptor mediated. Overall the results suggest that serotoninergic mechanisms contribute to some of the behavioural manifestations of hepatic encephalopathy in this animal model.
Yurdaydin
C
C
Department of Gastroenterology and Hepatology, University of Vienna, Austria.
Herneth
A M
AM
Püspök
A
A
Steindl
P
P
Singer
E
E
Ferenci
P
P
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006501:Hepatic Encephalopathy / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008784:Methysergide / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects; D010880:Piperidines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000502:physiology; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D013853:Thioacetamide
D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013853:Thioacetamide; C046301:seganserin; D012701:Serotonin; D008784:Methysergide