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Gender Affects Rats' Central Nervous System Histaminergic Responses to Dietary Manipulation^1,2,

Department of Nutrition and Food Science ^* Department of Psychiatry, University of Kentucky, Lexington, KY 40506-0054

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 K_D (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.

KEY WORDS: • receptor • growth • histamine • rats • gender • diet

¹ Supported by U.S. Department of Agriculture NRICGP Grant # 9400531 and the Agricultural Experiment Station, The University of Kentucky.

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ To whom correspondence and reprint requests should be addressed.

Manuscript received 21 September 1995. Revision accepted 29 August 1996.

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