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Brain Histamine Affects Eating and Drinking Behaviours

  • Leonardo Munari
  • Maria Beatrice Passani
Chapter

Abstract

Functional studies demonstrated that activation of the central histaminergic system alters brain functions in both behavioural and homeostatic contexts, which include sleep and wakefulness, learning and memory, anxiety, locomotion, feeding and drinking and neuroendocrine regulation. These actions are achieved through interactions with other neurotransmitter systems. Hence, numerous laboratories are pursuing novel compounds targeting the brain histaminergic receptors for various therapeutic indications. Preclinical studies are focusing on three major areas of interest and intense research is mainly oriented towards providing drugs for the treatment of sleep, cognitive and feeding disorders. The interest in the histaminergic system as a potential target for the treatment of feeding disorders is driven by the unsatisfactory history of the pharmacotherapy of obesity. The drugs currently available for long-term treatment of obesity (such as sibutramine, a monoamine re-uptake inhibitor, and orlistat, a peripherally acting lipase inhibitor) work by different mechanisms, reflecting the complex etiology of the disease. Often these medications achieve a rather modest degree of weight loss, and psychiatric and cardiovascular diseases are reported as adverse drug reactions. As a consequence, new molecular targets are being probed by academic and industrial research teams in the pursuit of novel treatments that may provide advantages over the currently available ones. The control of food intake and body weight is very complex and depends on the interplay of several central and peripheral neuroendocrine systems, environmental factors, the behavioural state and circadian rhythm, which all concur to alter homeostatic aspects of appetite and energy expenditure. Histaminergic activity shows a clear circadian rhythm with high levels during the active period and low levels during the sleep period and there is consistent evidence supporting a role of brain histamine in food intake and energy metabolism. Furthermore, brain histamine acts in concert with and complementary to reward systems, and learning circuits to influence appetitive and aversive behaviours. Brain histaminergic H1 receptors are crucial for the regulation of the diurnal rhythm of food intake and the regulation of obesity; however, from a therapeutic standpoint, no brain penetrating H1 receptor agonists have been identified that would have anti-obesity effects. Despite conflicting preclinical data, though insight are emerging into the potential role of histaminergic H3 receptor modulation as a target of anti-obesity therapeutics. Aim of this review is to outline the relevance of the histaminergic system in controlling feeding behaviour and to suggest the potential therapeutic use of histaminergic ligands for the treatment of feeding disorders.

Keywords

Thyrotropin Release Hormone Histaminergic Neurone Anorexigenic Effect Suppress Food Intake Histaminergic System 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

2-AG

2-Arachidonoylglicerol

ADH

Antidiuretic hormone

BAT

Brown adipose tissue

cGMP

Cyclic guanosine monophosphate

CNS

Central nervous system

FEO

Food-entrainable oscillator

GABA

Gamma-aminobutyric acid

GLP-1

Glucagon-like peptide 1

LH

Lateral hypothalamus

NAcc

Nucleus accumbens

PVN

Paraventricular nucleus

TMN

Tuberomammillary nucleus

TRH

Thyrotropin releasing hormon

Ucp-1

Uncoupling protein 1

VLPO

Ventrolateral preoptic area

VMH

Ventromedial hypothalamus

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Dipartimento di Farmacologia Preclinica e ClinicaUniversita’ di FirenzeFlorenceItaly

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