Histamine controls food intake in sheep via H1 receptors

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Abstract

Histamine is a well known amine which controls many physiological functions of the CNS, including fluid balance, appetite, thermoregulation, cardiovascular control, learning and the stress response. All these functions are mediated via three well known membrane receptors (H1, H2 and H3) and, in laboratory animals, feeding behavior is under the control of H1 type. In order to investigate the central effect of histamine on feeding behavior in sheep and the characterization of the receptor involved, two Latin square design experiments were undertaken using four Iranian Nainee rams implanted with intracerebroventricular cannulae. In the first experiment, 12 h fasted (7:00 p.m.–7:00 a.m.) rams in individual pens were infused with 0 (control), 100, 400 and 800 nM of histamine such that each ram received each dose four times on different days. Ten minutes after injection (7:00 a.m.) water and a food container were put in the pens and the consumption of water and food were recorded at 0.5, 1, 3 and 12 h. Results from this experiment revealed that histamine significantly (P < 0.01) suppressed food intake with no effect on water consumption. In the second experiment the use of three specific histamine antagonists: chloropheniramine, ranitidine and thioperamide, showed that the anorexic effect of histamine was significantly (P < 0.01) blocked by chloropheniramine. It is concluded that feeding behavior in sheep is inhibited by histamine acting via H1 receptors.

Introduction

Animal food intake and energy balance is an important topic in applied physiology. Using a variety of techniques the different mechanisms which control feeding behavior have been discovered. Many of these control mechanisms involve molecular signals from the periphery to the central nervous system (CNS), including glucose, triglycerides, leptin, insulin, amylin, enterostatin, ghrelin and cholecystokinin released from different tissues. These signals, in turn, modulate various transmitters in the CNS, such as neuropeptide Y, αMSH, opioids, interleukin 1, galanin, glutamate, dopamine, norepinephrine, serotonin, GABA, acetylcholine and histamine (Costentin, 2004).

Histamine is one of the well known amines which contribute in many physiological functions in the CNS (Brown et al., 2001), including feeding behavior (Cohn et al., 1973, Machidori et al., 1992, Ookuma et al., 1993). The two sources of this amine in the brain are neurons and mast cells (Garbarg et al., 1976), of which the latter are relatively scarce. Histaminergic neurons are almost exclusively localized in the tuberomammillary nucleus of the posterior hypothalamus and project to several brain areas (Inagaki et al., 1988). The released histamine has been shown to affect arousal state, locomotor activity, feeding and drinking functions (Cacabelos, 1990, Wada et al., 1991, Onodera et al., 1994, Doi et al., 1994) via three well known subtypes of H1, H2 and H3 receptors (Hill, 1990).

There is accumulating evidence to indicate that histamine inhibits food intake through H1 receptors (Sakata et al., 1988, Fukagawa et al., 1989, Ookuma et al., 1993, Doi et al., 1994, Lecklin et al., 1998). Research on different species, including rat (Lecklin et al., 1998), cat (Clineschmidt and Lotti, 1973) and goat (Tuomisto and Eriksson, 1979), have shown that histamine is involved in feeding behavior. Recent evidence suggests that leptin as an important antifeeding agent acts via histamine (Yoshimatsu et al., 1999, Itateyama et al., 2003), and supplementation of food with the histamine precursor histidine suppresses food intake in rats (Kasaoka et al., 2004). Sheep, as a ruminant model and a species different from laboratory animals, are under the influence of high concentration of circulating biogenic amines and are, therefore, of interest for studying the role of histamine. Thus, the present study was conducted to evaluate the central appetitive effects of histamine, its dose dependency, and its candidate receptors in the sheep brain.

Section snippets

Animals

Six 12-month-old Nainee (fat tailed, medium sized Iranian breed) male sheep weighing 32 ± 3 kg were used for this study. After 1 week of evaluation for health status, animals were implanted with an intracerebroventricular (ICV) cannula. Male sheep were selected since research has shown that the histamine content of mast cells in rat brain changes over the oestrous cycle (Aydin et al., 1998). The method for ICV cannulation was similar to the method described by Keverne and Kendrick (1992). Briefly,

Results

Results of the first experiment are shown in Table 1 and Fig. 1. In Table 1 water and food intake in the different time intervals after histamine infusion indicate that water consumption was not affected by any dose of histamine, but food intake was significantly (P < 0.01) reduced. At doses of 400 and 800 nM this effect persisted for at least 3 h with gradual recovery back to control levels; 100 nM of histamine was also effective on food intake level, however, this effect was only detected 0.5 h

Discussion

The role of histamine in fluid balance has been implicated for a long time. A direct action of histamine on drinking, mostly in laboratory animals, has been reported (Gerald and Maickel, 1972, Leibowitz, 1973), and an indirect effect of this amine on vasopressin has been confirmed (Bhargava et al., 1973, Bennet and Pert, 1974, Kjaer et al., 1994). However, the results of the present study show that water consumption in sheep was not influenced by any dose of histamine. These results, therefore,

Acknowledgments

The authors would like thank the Isfahan University of Technology (IUT) for financial support and Isfahan Medical University for generous gift of some drugs.

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