Manipulation of Central Nervous System Histamine or Histaminergic Receptors (H1) Affects Food Intake in Rats

Abstract

The reported studies were designed to examine relationships between central nervous system histamine, histaminergic receptors (H1) and food intake in rats. The hypothesis being tested was as follows: "One component of the neuroregulation of food intake involves histaminergic activity in the hypothalamus as influenced by variation of histamine levels and/or H1 receptor concentrations." We performed combinations of dietary, surgical and pharmacological treatments on male or female rats. We fed groups of male or female rats diets containing either 4 g casein/100 g diet (low protein diet) or 25 q casein/100 g diet (normal protein). Rats with surgical ablation of the paraventricular nucleus did not decrease food intake when fed the low protein diet, whereas adrenalectomized rats did. Increasing central histamine levels decreased food intake, whereas decreasing central histamine increased food intake. Rats injected with histaminergic (H1) antagonists lost the ability to detect low protein diet in short-term experiments and had improved efficiency of weight gain. Rats that were fed the low protein diet or pair-fed the normal protein diet had greater H1 receptor concentrations in whole brain preparations when compared with rats fed the normal protein diet. No differences were noted due to gender. Thus, manipulation of histamine levels affected food intake as hypothesized, i.e., increasing central histamine decreased food in rats fed the normal protein diet, whereas decreasing central histamine or blockade of H1 receptors increased food intake in rats fed the low protein diet.

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

“…[1][2][3][4] The very central function of neural histamine in regulation of food intake 1,[5][6][7] is further underlined by the fact that leptin, 8,9 amylin 10,11 and bombesin 12 have been suggested to exert their anorectic effects through histaminergic circuits. 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.…”

“…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.…”

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

“…The anorexigenic networks also project from ARC to PVN and are comprised of neurons coreleasing pro-opiomelanocortin, alphamelanocyte-stimulating hormone, brain-derived neurotrophic factor, and cocaine-and amphetamine-regulated transcript (Gerozissis, 2004;Kalra and Kalra, 2004;Saper et al, 2002;Schwartz and Porte, 2005). Orexin and melanin-concentrating hormone (MCH) from neurons in the lateral hypothalamus (LH) stimulate the orexigenic networks; ventromedial nucleus (VMN) exerts an opposite effect potentially via histaminergic mechanisms (Mercer et al, 1994;Sakata et al, 1997). Histamine also has an important role in catabolic processes by mediating the effects of leptin (Masaki et al, 2004), which promotes its release (Itateyama et al, 2003).…”

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

“…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).…”