Food Intake Is Inversely Correlated with Central Nervous System Histamine Receptor (H1) Concentrations in Male Sprague-Dawley Rats Fed Normal, Low Protein, Low Energy or Poor Quality Protein Diets

Haq, A.; Bundrant, Holly M.; Mercer, L. Preston

doi:10.1093/jn/126.12.3083

Cited by 21 publications

(24 citation statements)

References 24 publications

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“…In an interesting study Haq et al (1996), investigated the effects of dietary composition (quantity and quality of proteins and energetic level) on voluntary food intake and H 1 receptor expression in the whole brain. High concentration of H 1 receptors, as assessed with binding assays on tissue homogenate, was associated with decreased food intake of rats fed with a low protein diet.…”

Section: Interactions Between Central Histamine and Hormones In The Cmentioning

confidence: 99%

The histaminergic system as a target for the prevention of obesity and metabolic syndrome

2016

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Section: Interactions Between Central Histamine and Hormones In The Cmentioning

confidence: 99%

The histaminergic system as a target for the prevention of obesity and metabolic syndrome

2016

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“…In accordance herewith, histamineric neurons project into hypothalamic centres known to participate in food intake regulation: the paraventricular nucleus (PVN) and ventromedial hypothalamus (VMH), where the anorectic effect is thought to be mediated by postsynaptic histamine H 1 receptors. 5,13 The density of this receptor 14 together with the H 3 -receptor-mediated control of the intrasynaptic concentration of histamine both seem to be crucial for the strength of the anorectic signal. The intrasynaptic concentration of histamine is primarily controlled by feedback signals from presynaptic histamine H 3 receptors 15 that inhibit both the conversion of L-histidine to histamine 7 and the release of histamine into the synaptic cleft.…”

Section: Introductionmentioning

confidence: 99%

Influence of a selective histamine H3 receptor antagonist on hypothalamic neural activity, food intake and body weight

Malmlöf¹,

Zaragoza²,

Golozoubova³

et al. 2005

Int J Obes

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OBJECTIVE: This study was conducted to elucidate whether antagonistic targeting of the histamine H 3 receptor increases hypothalamic histamine levels, in parallel with decreases in food intake and body weight. METHODS:The competitive antagonist potency of a recently synthesized histamine H 3 receptor antagonist, NNC 38-1049, was studied in intact HEK293 cells expressing human or rat histamine H 3 receptor, in which NNC 38-1049 was allowed to antagonize the effect of the H 3 receptor agonist R-a-methylhistamine on isoprenaline-induced accumulation of cAMP. The affinity of NNC 38-1049 for a number of variants of the histamine receptor was also determined. Following single dosing of normal rats with NNC 38-1049, hypothalamic histamine levels were assessed by means of microdialysis. Plasma and brain levels of NNC 38-1049 and acute effects on food intake and energy expenditure were followed after oral doses of 3-60 mg/kg. Potential side effects were examined with rat models of behaviour satiety sequence (BSS), pica behaviour and conditioned taste aversion (CTA). Intakes of food and water together with body weight were recorded for 15 days during daily dosing of dietary obese rats. RESULTS: NNC 38-1049 was found to be a highly specific and competitive antagonist towards both human and rat histamine H 3 receptors, and measurable amounts of NNC 38-1049 were found in the plasma of rats following single oral doses of 3-60 mg/kg and in the brain after 15-60 mg/kg. Following single intraperitoneal injections of NNC 38-1049 (20 mg/kg), significant increases in extracellular histamine concentrations were observed. The same dose did not change BSS or pica behaviour acutely, nor did it induce CTA following repeated administration for 7 days. Reductions in food intake were seen very soon after administration, and occurred in a dose-dependent fashion. Energy expenditure was unchanged, but the respiratory quotient (RQ) tended to decrease at higher doses, indicating an increase in lipid oxidation. Twice daily administration of 20 mg/kg of NNC 38-1049 in old and dietary obese rats resulted in sustained reduction of food intake throughout a 2-week study, and was associated with a highly significant (Po0.01) decrease in body weight compared with controls (À18.473.4 vs þ 0.472.7 g). The same dose of NNC 38-1049 produced an acute decrease of water intake, but 24 h intakes were not significantly changed. CONCLUSIONS: The results of this study strongly support the idea that an increase in the hypothalamic concentration of histamine produces a specific reduction of food intake and that this effect can be translated into a decrease in body weight.

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“…Mercer et al (1994) showed that decreasing central histamine or blockade of H1 receptors increased food intake in rats fed the low protein diet (Mercer et al 1994). Similarly, Haq et al (1996) also found that the increased H1 receptors in the brain were closely correlated to the decrease in food intake, whereas decreases of H1 receptors were associated with an increase in food intake (Haq et al 1996). H1 receptor knockout (H1RKO) mice develop obesity accompanied by increased food intake and altered diurnal feeding patterns (Masaki et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Effects of simvastatin and 6-hydroxydopamine on histaminergic H1 receptor binding density in rat brains

Deng

Mackovski

et al. 2010

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Statins have been widely used for the treatment of a variety of medical conditions including psychoneurological disorders beyond their original use in lowering cholesterol. Histamine receptors play an important role in the regulation of neural activity, however, it is unknown whether statins act on histamine receptors, particularly for their neural regulatory effects. This study examined the effects of simvastatin and 6-hydroxydopamine (6-OHDA) lesions on histamine H1 receptors using [3H] pyrilamine binding autoradiography. Compared to the saline group, simvastatin (1 mg/kg/day) significantly decreased H1 receptor bindings in the primary motor cortex (M1), ventromedial hypothalamic nucleus (VMH), caudate putamen (CPu), accumbens core (AcbC) and prefrontal cortex (PfC) (all pb0.05); however 10 mg/kg/day simvastatin increased H1 receptor density only in the medial amygdaloid nucleus (Mep) (pb0.05), but had no significant effect in other regions examined. The 6-OHDA lesion did not alter H1 receptor binding density in most brain areas, except a trend decrease in the hippocampus (p=0.07) and a trend increase in the cingulate cortex (p=0.06). These results suggested that simvastatin has different effects on the H1 receptors in different rat brain regions depending on the doses. Therefore, simvastatin can modulate histaminergic neurotransmission in the brain, and support the role of H1 receptors in psychoneurological disorders.

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Food Intake Is Inversely Correlated with Central Nervous System Histamine Receptor (H1) Concentrations in Male Sprague-Dawley Rats Fed Normal, Low Protein, Low Energy or Poor Quality Protein Diets

Cited by 21 publications

References 24 publications

The histaminergic system as a target for the prevention of obesity and metabolic syndrome

The histaminergic system as a target for the prevention of obesity and metabolic syndrome

Influence of a selective histamine H3 receptor antagonist on hypothalamic neural activity, food intake and body weight

Effects of simvastatin and 6-hydroxydopamine on histaminergic H1 receptor binding density in rat brains

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