Gender Affects Rats' Central Nervous System Histaminergic Responses to Dietary Manipulation

Abstract

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.