Neocortical Dialysate Monoamines of Rats After Acute, Subacute, and Chronic Liver Shunt

Abstract

Intracerebral microdialysis was applied to monitor the neocortical extracellular levels of the aromatic amino acids phenylalanine, tyrosine, and tryptophan, the neurotransmitters dopamine (DA), noradrenaline (NA), and serotonin (5‐HT), and the metabolites 3,4‐dihydroxyphenylacetic acid (DOPAC) and 5‐hydroxyindole‐3‐acetic acid (5‐HIAA) in rats with various forms of experimental hepatic encephalopathy (HE). The extracellular aromatic amino acid levels were clearly increased in acute, subacute, and chronic HE. No changes compared with controls in the neocortical DA release could be detected in the three experimental HE rat models investigated. The NA release showed a significant increase only in the subacute HE group. These data suggest that HE may not be associated with any major reduction of neocortical DA or NA release as previously suggested. In acute and subacute HE, decreased extracellular DOPAC but elevated 5‐HIAA concentrations were seen. In chronic HE, elevations of both DOPAC and 5‐HIAA were observed. Neocortical 5‐HT release did not change in subacute and chronic HE, whereas it decreased in acute HE compared with control values. Significant increase in extracellular concentrations of 5‐HIAA and of the 5‐HIAA/5‐HT ratio in the present study are in agreement with previously reported increases in 5‐HT turnover in experimental HE. However, a substantially increased 5‐HT turnover in experimental HE does not appear to be related to an increase in neuronal neocortical 5‐HT release.

Fatigue of cholestasis and the serotoninergic neurotransmitter system in the rat†

“…These results suggest that 5-HT metabolism is increased in rats with BDR with essentially unchanged basal 5-HT output, similar to the situation in more severe liver disease with hepatic encephalopathy. 25,26 The possibility that neuronal output is actually increased but that an enhanced 5-HT uptake compensates for the change in release-thus maintaining the extracellular level at a more or less constant levelcannot be ruled out. Overall, these findings argue against a functional overactivity of the serotoninergic system as a potential cause of the fatigue associated with cholestasis.…”

Sustained Citalopram Treatment in Experimental Hepatic Encephalopathy: Effects on Entrainment to the Light‐Dark Cycle and Melatonin

“…Disturbances in the CNS monoaminergic systems, notably the 5‐HT innervated system, have received much attention in hepatic encephalopathy research over the years (Bengtsson 1992; Mousseau & Butterworth 1994; Bengtsson et al 1997), and several investigations have shown increased 5‐HT metabolism the CNS. Hence, both increased levels of 5‐HT and its metabolite 5‐hydroxyindole‐3‐acetic acid (5‐HIAA) have been shown in cerebrospinal fluid of patients suffering from chronic hepatic encephalopathy (Borg et al 1982; Rössle et al 1984) as well as in experimental chronic hepatic encephalopathy (Bengtsson et al 1985; Bergeron et al 1990; Bergqvist et al 1995). The pineal 5‐HT metabolite melatonin has also been reported to be altered in chronic hepatic encephalopathy, in turn tentatively related to an altered diurnal rhythm in this condition (Zee et al 1991; Steindl et al 1995a).…”

Sustained administration of the antidepressant venlafaxine in rats: pharmacokinetic and pharmacodynamic findings

“…The dialysate 5-HT and 5-HIAA contents were determined by using HPLC with electrochemical detection according to a method described by Hjorth and Sharp (1993) with minor modifications (Bergqvist et al 1995). In short, the dialysis samples were directly injected with a Rheodyne 7125 injector (Rheodyne, Cotati, Calif., USA).…”

“…The dialysate noradrenaline and dopamine levels were determined by a radioenzymatic method (Peuler and Johnson 1977;Schmidt et al 1982) with some modifications (Kalén et al 1988;Bergqvist et al 1995). In brief, 25 µl of the dialysates was transferred to tubes containing 5 µl 1 mol/l TRIS base, 5 µl 300 mmol/l MgCl 2 , 2.5 µl 200 mmol/l EGTA, 4 µl catechol-O-methyltransferase (prepared from rat liver) enzyme solution, 2.1 µl dithiothreitol/pargyline mix (0.105 mol/l and 25 mmol/l, respectively), and 1 µl S-adenosyl-L-[methyl-3 H]methionin (TRK 581, 60-85 Ci/mmol; Amersham Sweden, Solna, Sweden).…”