The reported studies were designed to examine relationships between whole-brain histamine receptors (H1) and food intake in male Sprague-Dawley rats. Three different experiments were conducted. In each experiment, control rats were fed normal protein (25 g casein/100 g food) and normal metabolizable energy (16.21 kJ/100 g food) diets. Feeding low protein diets (1 g casein/100 g food) elevated central H1 receptor concentrations (P < 0.0027) and reduced voluntary food intake (P < 0.007) compared with normal diets. Feeding low energy diets lowered H1 receptor concentrations (P < 0.0089) and increased voluntary food intake (P < 0.0012). Low quality protein diets also affected the central nervous histaminergic system. Whole-brain H1 receptor concentrations were significantly higher for rats fed low quality protein (25 g gelatin/100 g food) compared with rats fed casein (P < 0.0001). Rats fed medium quality protein (25 g wheat gluten/100 g food) or low quality protein ate significantly less food (P < 0.0001). In all experiments, dietary manipulation affected central histamine receptors. Elevated concentrations of H1 receptors were associated with a decrease in food intake whereas lowered concentrations of H1 receptors were associated with an increase in food intake (P < 0.001). The results of these experiments support the hypothesis that central histamine H1 receptor concentrations in male rats are inversely correlated with voluntary food intake and affected by dietary composition.

The histaminergic system (histamine and its H1-receptor) of the central nervous system has been implicated in control of food intake. The reported studies were designed to examine the effects of food restriction and very low (1%) protein diets on central nervous system H1-receptors in male and female rats. In a series of experiments, groups of rats were freely fed a 25% protein diet, a 1% protein diet, or fed the 25% protein diet at 4 g/100 g body weight for 14-20 d. When freely fed 25% protein diets, females had higher whole-brain H1-receptor binding than males on d 1 (female 122.36 +/- 4.53 and male 65.78 +/- 3.82 pmol/g protein; P < 0.001). Changing diets affected central H1-receptor binding in both males and females (P < 0.003). When rats were fed both restricted levels of food and 1% protein diets, the receptor binding of males increased by d 5 whereas that of females decreased by d 5 (P < 0.001). When fed 1% protein diets, females had decreased H1-receptor binding (98.4 +/- 2.38 pmol/g protein) and that in males increased to 119.81 +/- 5.09 pmol/g protein. After 15 d, females had eaten significantly more food than males: females 166 +/- 4.9 g, males 124 +/- 1.9 g (P< 0.0007). Males had a significantly greater weight loss than females: males -28.8 +/- 2.6 g, females -17.08 +/- 0.97 g (P < 0.0007). When fed restricted diets, females had decreased H1-receptor binding (93.81 +/- 5.58 pmol/g) whereas binding in males increased to 111.27 +/- 8.55 pmol/g. Preliminary saturation binding studies indicated that restricted food intake lowered receptor density (females consuming 25% protein: 715 +/- 30 pmol/g protein; female restricted: 467 +/- 28 pmol/g protein, P < 0.05), while 1% protein increased receptor sensitivity, i.e., lowered KD (males consuming 25% protein: 15.3 +/- 1.8 nmol; males fed low protein: 2.8 +/- 0.27 nmol). This study suggests that dietary manipulation affects central H1-receptor binding in a gender-specific manner, thereby modulating central histaminergic activity during food or protein deficit.

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