Brain histamine affects eating and drinking behaviour

In the early 1980s two major discoveries convinced the scientific community of the existence of a central histaminergic system and contributed to the understanding of its many functions. Immunohistochemical studies demonstrated the localization of histaminergic neurones in the tuberomammillary nuclei of the posterior hypothalamus with projections to almost all parts of the brain (Panula et al. 1984; Watanabe et al. 1984), and pharmacological studies proved the existence of a novel histaminergic autoreceptor, the H3 receptor (Arrang et al. 1983). A plethora of neuropharmacological and behavioural studies ensued and it soon became clear that brain histamine affects a variety of homeostatic regulatory functions such as circadian rhythms, neuroendocrine secretion, food intake, body weight and drinking. Furthermore, it was soon proven that histamine-containing neurones constitute a major wake-promoting system because their terminals influence neuronal excitability in distinct brain regions. Wakefulness is a prerequisite for learning and memorising salient events, but there is ample evidence that the histaminergic system affects cognitive functions per se. These observations are relevant for feeding behaviour, both for food searching and food consumption, as the ability to remember the context associated with food availability or the palatability of the food eaten provides a clear adaptive advantage to animal foraging. Hence, brain histamine does not only provide a satiety signal released during eating that might integrate postprandial messages conveyed from peripheral tissues (e.g. leptin), but it is important in setting up circadian homeostatic functions that create the expectations for a meal and coordinate food searching strategies. In other words, evidence indicates that histaminergic neurones control both the appetitive, or food searching, behaviour and the consummatory phases of feeding. However, very few experiments have dealt with this issue. The association of histamine with feeding behaviour became clear when it was observed that antidepressants and antipsychotics stimulate appetite and induce weight gain and that these drugs are potent H1 receptor blockers. Indeed, early studies showed that intracerebral injections of histamine depressed the feeding behaviour of rats (Clineschmidt and Lotti 1973), while microinjections of the histaminergic H1 receptor antagonists in the ventromedial hypothalamus (VMH) elicit feeding. Recent observations, though, indicate that histamine release during feeding is better interpreted in the context of appetitive rather than the consummatory phase of feeding behaviour (Meynard et al. 2005). We now know that brain histamine is involved in feeding physiology by modulating the release of neurotransmitters and hormones that drive or inhibit feeding (Toftegaard et al. 2003). In addition, to exert their orexigenic or anorexigenic effects, hormones and peptides require an intact histaminergic system. Hence, in addition to having an effect on food intake, brain histamine regulates body weight by modulating peripheral energy metabolism in rodents. Also, compulsive eating in anorexia nervosa, bulimia, or binge-eating syndrome likely relates to histamine effects on brain reward systems and learning circuits and their dysfunction in addiction.