Long‐Term Effects of Portacaval Anastomosis on the 5‐Hydroxytryptamine, Histamine, and Catecholamine Neurotransmitter Systems in Rat Brain

Abstract

Portacaval anastomosis (PCA) in the rat is used as a model for portal systemic encephalopathy. Changes in the serotonergic, histaminergic, and catecholaminergic neurotransmitter systems are often found shortly after PCA. We have examined the long‐term effects of PCA on the aminergic systems in brains of male Wistar rats, which 8 months previously had been subjected to PCA. Precursors, amines, and metabolites were assayed by HPLC. Eight months after PCA, the catecholamine levels were unchanged in all brain regions. In contrast, tryptophan was evenly increased throughout the brain. The accumulation of 5‐hydroxytryptophan after decarboxylase inhibition (NSD‐1015; 100 mg/kg i.p.) and the endogenous levels of 5‐hydroxyindoleacetic acid were significantly higher in PCA rats, particularly in the hypothalamus and midbrain, whereas 5‐hydroxytryptamine concentrations were unchanged. Histamine levels were elevated throughout the brain with the greatest increase found in the hypothalamus and in the striatum. tele‐Methylhistamine levels were significantly elevated in cortex and hypothalamus. We conclude that 8 months after PCA, catecholaminergic systems had reestablished their homeostasis, whereas serotonergic and histaminergic systems still show profound disturbances in their function. With histamine, this is reflected as an increase in the amounts of both transmitter and metabolite; serotonergic neurons respond by increasing only the level of the metabolite.

Increased brain serotonin turnover correlates with the degree of shunting and hyperammonemia in rats following variable portal vein stenosis

“…4) [36]. However, in agreement with previous observations using PCA rats [7,37,38], the present study did not demonstrate any significant changes in Fig. 3.…”

Neuronal storage of histamine in the brain and tele‐methylimidazoleacetic acid excretion in portocaval shunted rats

“…However, any increase in amine synthesis in the CNS is effectively counteracted by at least two distinct mechanisms namely, increased degradation (serotonin, dopamine, histamine) and intracellular deposition (histamine only) (Fogel et al . 1991a,b, 1994; Lozeva et al . 1998).…”

“…The rats were killed by decapitation and, in order to slow down the postmortem metabolism, the heads were immediately immersed for 3 s in liquid nitrogen to cool, but not freeze, the brain (Lozeva et al . 1998).…”

“…In rats, several months after portocaval shunt, more N ‐ tele ‐methylhistamine is found in some brain areas suggesting that concurrent to neural deposition further adaptional change involves an increase in histamine degradation (Lozeva et al . 1995, 1998).…”

Increased density of brain histamine H1 receptors in rats with portacaval anastomosis and in cirrhotic patients with chronic hepatic encephalopathy

“…Among the least exploited consequences of HE are the marked changes in the brain histaminergic system, which have been previously documented both in patients with HE 3 and in rats with portacaval anastomosis (PCA), a well-established animal model of the disease. [4][5][6][7][8] There is substantial evidence that histamine acts as a neurotransmitter in mammalian brain. 9 Histaminergic neurons are located exclusively in the tuberomammillary nucleus of the posterior hypothalamus and send their varicose fibers to almost every region of the brain.…”