The manipulation of brain histamine concentrations failed to modify voluntary alcohol intake by rats

Abstract

IntroductionPortocaval anastomosis (PCA) induces chronic liver failure with resulting well characterised metabolic consequences. The blood levels of potentially cerebrotoxic substances is greatly increased. There are also increased concentrations of aromatic amino acids, neurotransmitter precursors: TRY, PHE, TYR, HIS, which freely penetrate the blood-brain barrier. In the CNS an enhanced synthesis of neurotransmitters is facilitated. The excessive amine formation is counterbalanced either by increased catabolism (5HT, dopamine) or deposition (histamine) as demonstrated by increased cerebral indoleamine and catecholamine metabolite levels and of histamine, respectively [1,2]. The liver is the organ chiefly responsible for alcohol metabolism. Interestingly, rats with chronic liver failure caused by PCA show a higher preference for alcohol than their sham operated pairs [3,4]. The mechanism involved in the development of abnormal alcohol drinking by PCA rats remains unknown. As histamine has been shown to influence diuresis, thermoregulation and EEG activity, hypothalamic functions, which are also affected by ethanol a possible contribution of altered brain histamine system was examined. Materials and methodsWistar outbred rats with surgically constructed portocaval anastomosis (PCA) and confirmed altered hepatic function as well as sham operated controls were used. Animal procedures complied with Polish legislation concerning experiments on animals and were approved by the local care committee. To reveal the link between cerebral histamine concentration and voluntary alcohol intake, treatments were applied to decrease the high histamine concentration in PCA brains and to increase it in control animals [5]. Accordingly, alfa-fluoromethylhistidine, 50 mg/kg and L-histidine, 1000 mg/kg were used. Both these drugs were given s. c. at the beginning of dark phase of the 24 h cycle for 3 consecutive days. Throughout the experiments rats were kept in metabolic cages and had a free access to fluids: water and 10% ethyl alcohol as well as to food. The consumption and excretion were recorded daily. Results and discussionThe results are presented in Table 1. Shunted rats, although weighing less (329 ± 13 vs. 476 ± 33 g, p < 0.05), ate and drank significantly more (p < 0.05 at least) than sham rats. They also excreted more urine (p < 0.01). When given a free choice between water and 10% ethyl alcohol they preferred ethanol. Alcohol accounted for about 65-70% of fluids consumed by these animals, whilst only for about 20-25% by the controls. These data are fully in agreement with our previously published results [3,4] showing an increased alcohol preference associated with liver function impairment. Indeed, at autopsy the liver size was about 40% less in PCA rats as compared to their control counterparts. Atrophy was evident when measures were expressed in terms of liver index (liver weight to body weight ratio ¥ 100). For shunted rats the calculated liver index was 1.755 ± 0.06 (mean ± SEM) whereas it was 2.920 ± 0.090 for sham...

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

“…These data agree well with findings that excretion of histamine or metabolites, indicative of whole body histamine formation, was reduced to one-third or less in rats and humans after total gastrectomy or on total parenteral nutrition (Lundel 1974;Imamura et al 1984;Lö nroth et al 1990) and was significantly enhanced after histamine load (Granerus 1968;Keyzer et al 1984). It should be noted that under a standardized diet ad libitum PCA rats usually ate more feed (Fogel et al 1999b). However, the histamine concentration of the feed was negligible and even large amounts of L-histidine consumed would not affect urinary excretion of t-MeImAA (Granerus 1968).…”

“…1984). It should be noted that under a standardized diet ad libitum PCA rats usually ate more feed (Fogel et al . 1999b).…”