The histaminergic network in the brain: Basic organization and role in disease

Nature Reviews Neuroscience

Volumn 14, Issue 7, 2013, Pages 472-487

  Panula, Pertti ^a   Nuutinen, Saara ^a  

^a UNIVERSITY OF HELSINKI   (Finland)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID; 5 HYDROXYTRYPTOPHAN; AMPHETAMINE; APOMORPHINE; CIPROXIFAN; COCAINE; DYNORPHIN; FAMOTIDINE; GALANIN; GHRELIN; HALOPERIDOL; HISTAMINE; HISTAMINE H3 RECEPTOR; HISTAMINE RECEPTOR; IMIDAZOLE; LEPTIN; LEVODOPA; MESSENGER RNA; METHAMPHETAMINE; MUSCIMOL; PLACEBO; QUINPIROLE; THIOPERAMIDE;

ADDICTION; ALLERGIC ENCEPHALOMYELITIS; BRAIN DEVELOPMENT; BRAIN DYSFUNCTION; CEREBELLUM CORTEX; GILLES DE LA TOURETTE SYNDROME; HIPPOCAMPUS; HISTAMINE RELEASE; HUMAN; IMMUNOFLUORESCENCE; IMMUNOREACTIVITY; MAMMAL; MULTIPLE SCLEROSIS; NARCOLEPSY; NERVE CELL NETWORK; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; REVIEW; SCHIZOPHRENIA; SIGNAL TRANSDUCTION; SLEEP; WAKEFULNESS;

ANIMALS; BRAIN; HISTAMINE; HUMANS; NERVOUS SYSTEM DISEASES; NEURAL PATHWAYS; NEUROTRANSMITTER AGENTS; WAKEFULNESS;

MAMMALIA;

EID: 84879367045     PISSN: 1471003X     EISSN: 14710048     Source Type: Journal    
DOI: 10.1038/nrn3526     Document Type: Review

References (204)

1. Panula, P., Yang, H. Y. & Costa, E. Histamine-containing neurons in the rat hypothalamus. Proc. Natl Acad. Sci. USA 81, 2572-2576 (1984).
2. Watanabe, T. et al. Distribution of the histaminergic neuron system in the central nervous system of rats; a fluorescent immunohistochemical analysis with histidine decarboxylase as a marker. Brain Res. 295, 13-25 (1984). (Pubitemid 14155851)
3. Haas, H. & Panula, P. The role of histamine and the tuberomamillary nucleus in the nervous system. Nature Rev. Neurosci. 4, 121-130 (2003). (Pubitemid 37271382)
4. Haas, H. L., Sergeeva, O. A. & Selbach, O. Histamine in the nervous system. Physiol. Rev. 88, 1183-1241 (2008).
5. Anichtchik, O. V., Rinne, J. O., Kalimo, H. & Panula, P. An altered histaminergic innervation of the substantia nigra in Parkinson's disease. Exp. Neurol. 163, 20-30 (2000). (Pubitemid 30314356)
6. Ercan-Sencicek, A. G. et al. L-histidine decarboxylase and Tourette's syndrome. N. Engl. J. Med. 362, 1901-1908 (2010).
7. 4 receptors in autoimmune inflammatory disease of the central nervous system. Eur. J. Immunol. 42, 1536-1546 (2012).
8. Tuomisto, L. & Panula, P. in Histaminergic Neurons: Morphology and Function (eds Watanabe, T. & Wada, H.) 177-192 (CRC Press, 1991).
9. Airaksinen, M. S. et al. Histamine neurons in human hypothalamus: anatomy in normal and Alzheimer diseased brains. Neuroscience 44, 465-481 (1991).
10. Ericson, H., Watanabe, T. & Kohler, C. Morphological analysis of the tuberomammillary nucleus in the rat brain: delineation of subgroups with antibody against L-histidine decarboxylase as a marker. J. Comp. Neurol. 263, 1-24 (1987). (Pubitemid 17122461)
11. Panula, P. et al. The comparative neuroanatomy and neurochemistry of zebrafish CNS systems of relevance to human neuropsychiatric diseases. Neurobiol. Dis. 40, 46-57 (2010).
12. Sundvik, M. et al. The histaminergic system regulates wakefulness and orexin/hypocretin neuron development via histamine receptor H1 in zebrafish. FASEB J. 25, 4338-4347 (2011).
13. Sundvik, M., Chen, Y. C. & Panula, P. Presenilin1 regulates histamine neuron development and behavior in zebrafish, Danio rerio. J. Neurosci. 33, 1589-1597 (2013).
14. Panula, P., Pirvola, U., Auvinen, S. & Airaksinen, M. S. Histamine-immunoreactive nerve fibers in the rat brain. Neuroscience 28, 585-610 (1989). (Pubitemid 19081018)
15. Miklos, I. H. & Kovacs, K. J. Functional heterogeneity of the responses of histaminergic neuron subpopulations to various stress challenges. Eur. J. Neurosci. 18, 3069-3079 (2003). (Pubitemid 38021548)
16. Blandina, P., Munari, L., Provensi, G. & Passani, M. B. Histamine neurons in the tuberomamillary nucleus: a whole center or distinct subpopulations? Front. Syst. Neurosci. 6, 33 (2012).
17. Giannoni, P. et al. Heterogeneity of histaminergic neurons in the tuberomammillary nucleus of the rat. Eur. J. Neurosci. 29, 2363-2374 (2009).
18. Arrang, J. M., Garbarg, M. & Schwartz, J. C. Autoinhibition of brain histamine release mediated by a novel class (H3) of histamine receptor. Nature 302, 832-837 (1983). (Pubitemid 13125123)
19. Arrang, J. M. et al. Highly potent and selective ligands for histamine H3-receptors. Nature 327, 117-123 (1987).
20. Yamamoto, Y., Mochizuki, T., Okakura-Mochizuki, K., Uno, A. & Yamatodani, A. Thioperamide, a histamine H3 receptor antagonist, increases GABA release from the rat hypothalamus. Methods Find. Exp. Clin. Pharmacol. 19, 289-298 (1997). (Pubitemid 27397604)
21. +-evoked release of acetylcholine from rat cortex in vivo. Inflamm. Res. 45, S54-S55 (1996). (Pubitemid 26097486)
22. + ions, G protein and adenylate cyclase. Naunyn Schmiedebergs Arch. Pharmacol. 350, 34-41 (1994).
23. 3 agonist immepip and systemic apomorphine elicit ipsilateral turning behaviour in naive rats, but reduce contralateral turning in hemiparkinsonian rats. Behav. Brain Res. 154, 409-415 (2004). (Pubitemid 39093991)
24. 3H]-γ-aminobutryic acid from rat striatal slices. Br. J. Pharmacol. 133, 165-171 (2001). (Pubitemid 32500463)
25. 2 receptors and the implications for striatal function. Neuropharmacology 55, 190-197 (2008).
26. 4 receptor is functionally expressed on neurons in the mammalian CNS. Br. J. Pharmacol. 157, 55-63 (2009).
27. 3 isoform confers pharmacological differences and constitutive activity. J. Pharmacol. Exp. Ther. 323, 888-898 (2007). (Pubitemid 350146058)
28. 3 receptor isoforms with different brain expression and signaling properties. Mol. Pharmacol. 59, 1-8 (2001). (Pubitemid 32043078)
29. Takeshita, Y. et al. Histamine modulates high-voltage-activated calcium channels in neurons dissociated from the rat tuberomammillary nucleus. Neuroscience 87, 797-805 (1998). (Pubitemid 28400350)
30. Saper, C. B., Scammell, T. E. & Lu, J. Hypothalamic regulation of sleep and circadian rhythms. Nature 437, 1257-1263 (2005). (Pubitemid 41568665)
31. Takahashi, K., Lin, J. S. & Sakai, K. Neuronal activity of histaminergic tuberomammillary neurons during wake-sleep states in the mouse. J. Neurosci. 26, 10292-10298 (2006). (Pubitemid 44527422)
32. Lin, J. S., Sakai, K., Vanni-Mercier, G. & Jouvet, M. A critical role of the posterior hypothalamus in the mechanisms of wakefulness determined by microinjection of muscimol in freely moving cats. Brain Res. 479, 225-240 (1989). (Pubitemid 19035906)
33. Zecharia, A. Y. et al. GABAergic inhibition of histaminergic neurons regulates active waking but not the sleep-wake switch or propofol-induced loss of consciousness. J. Neurosci. 32, 13062-13075 (2012).
34. Lin, J. S., Sakai, K. & Jouvet, M. Evidence for histaminergic arousal mechanisms in the hypothalamus of cat. Neuropharmacology 27, 111-122 (1988). (Pubitemid 18052351)
35. Sakai, K., Takahashi, K., Anaclet, C. & Lin, J. S. Sleep-waking discharge of ventral tuberomammillary neurons in wild-type and histidine decarboxylase knock-out mice. Front. Behav. Neurosci. 4, 53 (2010).
36. Xu, C. Q. et al. Histamine innervation and activation of septohippocampal GABAergic neurones: involvement of local ACh release. J. Physiol. 561, 657-670 (2004).
37. Lin, J. S., Hou, Y., Sakai, K. & Jouvet, M. Histaminergic descending inputs to the mesopontine tegmentum and their role in the control of cortical activation and wakefulness in the cat. J. Neurosci. 16, 1523-1537 (1996). (Pubitemid 26145931)
38. Kiviranta, T., Tuomisto, L. & Airaksinen, E. M. Diurnal and age-related changes in cerebrospinal fluid tele-methylhistamine levels during infancy and childhood. Pharmacol. Biochem. Behav. 49, 997-1000 (1994). (Pubitemid 24376041)
39. Zant, J. C., Rozov, S., Wigren, H. K., Panula, P. & Porkka-Heiskanen, T. Histamine release in the basal forebrain mediates cortical activation through cholinergic neurons. J. Neurosci. 32, 13244-13254 (2012).
40. Ellender, T. J., Huerta-Ocampo, I., Deisseroth, K., Capogna, M. & Bolam, J. P. Differential modulation of excitatory and inhibitory striatal synaptic transmission by histamine. J. Neurosci. 31, 15340-15351 (2011).
41. McCormick, D. A. & Williamson, A. Modulation of neuronal firing mode in cat and guinea pig LGNd by histamine: possible cellular mechanisms of histaminergic control of arousal. J. Neurosci. 11, 3188-3199 (1991).
42. Sakurai, T. et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92, 573-585 (1998). (Pubitemid 28101119)
43. de Lecea, L. et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc. Natl Acad. Sci. USA 95, 322-327 (1998). (Pubitemid 28103952)
44. Peyron, C. et al. Neurons containing hypocretin (orexin) project to multiple neuronal systems. J. Neurosci. 18, 9996-10015 (1998). (Pubitemid 28543775)
45. Kaslin, J., Nystedt, J. M., Ostergard, M., Peitsaro, N. & Panula, P. The orexin/hypocretin system in zebrafish is connected to the aminergic and cholinergic systems. J. Neurosci. 24, 2678-2689 (2004). (Pubitemid 38380944)
46. Anaclet, C. et al. Orexin/hypocretin and histamine: distinct roles in the control of wakefulness demonstrated using knock-out mouse models. J. Neurosci. 29, 14423-14438 (2009).
47. Eriksson, K. S., Sergeeva, O., Brown, R. E. & Haas, H. L. Orexin/hypocretin excites the histaminergic neurons of the tuberomammillary nucleus. J. Neurosci. 21, 9273-9279 (2001). (Pubitemid 33096871)
48. Bayer, L. et al. Orexins (hypocretins) directly excite tuberomammillary neurons. Eur. J. Neurosci. 14, 1571-1575 (2001). (Pubitemid 35463724)
49. Yamanaka, A. et al. Orexins activate histaminergic neurons via the orexin 2 receptor. Biochem. Biophys. Res. Commun. 290, 1237-1245 (2002). (Pubitemid 34694437)
50. Huang, Z. L. et al. Arousal effect of orexin A depends on activation of the histaminergic system. Proc. Natl Acad. Sci. USA 98, 9965-9970 (2001).
51. Ishizuka, T., Murotani, T. & Yamatodani, A. Modanifil activates the histaminergic system through the orexinergic neurons. Neurosci. Lett. 483, 193-196 (2010).
52. Lin, L. et al. Measurement of hypocretin/orexin content in the mouse brain using an enzyme immunoassay: the effect of circadian time, age and genetic background. Peptides 23, 2203-2211 (2002). (Pubitemid 36092055)
53. Heller, H. C. & Ruby, N. F. Sleep and circadian rhythms in mammalian torpor. Annu. Rev. Physiol. 66, 275-289 (2004). (Pubitemid 40614446)
54. Sallmen, T. et al. Major changes in the brain histamine system of the ground squirrel Citellus lateralis during hibernation. J. Neurosci. 19, 1824-1835 (1999). (Pubitemid 29094198)
55. Sallmen, T., Lozada, A. F., Beckman, A. L. & Panula, P. Intrahippocampal histamine delays arousal from hibernation. Brain Res. 966, 317-320 (2003). (Pubitemid 36255596)
56. Nikmanesh, F. G., Spangenberger, H. & Igelmund, P. Histamine enhances synaptic transmission in hippocampal slices from hibernating and warm-acclimated Turkish hamsters. Neurosci. Lett. 210, 119-120 (1996). (Pubitemid 26180130)
57. Kukko-Lukjanov, T. K. et al. Histaminergic neurons protect the developing hippocampus from kainic acid-induced neuronal damage in an organotypic coculture system. J. Neurosci. 26, 1088-1097 (2006).
58. Tamura, Y., Monden, M., Shintani, M., Kawai, A. & Shiomi, H. Neuroprotective effects of hibernation-regulating substances against low-temperature-induced cell death in cultured hamster hippocampal neurons. Brain Res. 1108, 107-116 (2006). (Pubitemid 44278005)
59. Alvarez, E. O. The role of histamine on cognition. Behav. Brain Res. 199, 183-189 (2009).
60. Pollard, H., Moreau, J., Arrang, J. M. & Schwartz, J. C. A detailed autoradiographic mapping of histamine H3 receptors in rat brain areas. Neuroscience 52, 169-189 (1993). (Pubitemid 23026616)
61. Martinez-Mir, M. I. et al. Three histamine receptors (H1, H2 and H3) visualized in the brain of human and non-human primates. Brain Res. 526, 322-327 (1990). (Pubitemid 20307895)
62. de Almeida, M. A. & Izquierdo, I. Memory facilitation by histamine. Arch. Int. Pharmacodyn. Ther. 283, 193-198 (1986). (Pubitemid 16000248)
63. de Almeida, M. A. & Izquierdo, I. Intracerebroventricular histamine, but not 48/80, causes posttraining memory facilitation in the rat. Arch. Int. Pharmacodyn. Ther. 291, 202-207 (1988). (Pubitemid 18068238)
64. Dai, H. et al. Selective cognitive dysfunction in mice lacking histamine H1 and H2 receptors. Neurosci. Res. 57, 306-313 (2007). (Pubitemid 46177303)
65. -/- mice. Eur. J. Neurosci. 19, 1992-1996 (2004). (Pubitemid 38482588)
66. Dere, E. et al. Histidine-decarboxylase knockout mice show deficient nonreinforced episodic object memory, improved negatively reinforced water-maze performance, and increased neo-and ventro-striatal dopamine turnover. Learn. Mem. 10, 510-519 (2003). (Pubitemid 37499779)
67. -/-) mice. Brain Res. 1071, 113-123 (2006). (Pubitemid 43255482)
68. Liu, L. et al. Improved learning and memory of contextual fear conditioning and hippocampal CA1 long-term potentiation in histidine decarboxylase knock-out mice. Hippocampus 17, 634-641 (2007). (Pubitemid 47292034)
69. Chepkova, A. et al. Histamine receptor expression, hippocampal plasticity and ammonia in histidine decarboxylase knockout mice. Cell. Mol. Neurobiol. 32, 17-25 (2012).
70. -/-) mice. Behav. Brain Res. 168, 92-99 (2006). (Pubitemid 43153771)
71. Horvath, T. L. & Diano, S. The floating blueprint of hypothalamic feeding circuits. Nature Rev. Neurosci. 5, 662-667 (2004). (Pubitemid 39013597)
72. Saper, C. B., Chou, T. C. & Elmquist, J. K. The need to feed: homeostatic and hedonic control of eating. Neuron 36, 199-211 (2002). (Pubitemid 35217887)
73. Gillum, M. P. et al. N-acylphosphatidylethanolamine, a gut-derived circulating factor induced by fat ingestion, inhibits food intake. Cell 135, 813-824 (2008).
74. Dietrich, M. O. & Horvath, T. L. Feeding signals and brain circuitry. Eur. J. Neurosci. 30, 1688-1696 (2009).
75. 1 receptors in rats: potential involvement of E3 subgroup of histaminergic neurons in tuberomammillary nucleus. Brain Res. 1387, 61-70 (2011).
76. Kroeze, W. K. et al. H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. Neuropsychopharmacology 28, 519-526 (2003).
77. Inzunza, O., Seron-Ferre, M. J., Bravo, H. & Torrealba, F. Tuberomammillary nucleus activation anticipates feeding under a restricted schedule in rats. Neurosci. Lett. 293, 139-142 (2000).
78. Angeles-Castellanos, M., Aguilar-Roblero, R. & Escobar, C. c-Fos expression in hypothalamic nuclei of food-entrained rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 286, R158-R165 (2004). (Pubitemid 38055905)
79. 3 receptor and eating behavior. J. Pharmacol. Exp. Ther. 336, 24-29 (2011).
80. Zhang, Y. et al. Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425-432 (1994). (Pubitemid 24365442)
81. Elmquist, J. K., Bjorbaek, C., Ahima, R. S., Flier, J. S. & Saper, C. B. Distributions of leptin receptor mRNA isoforms in the rat brain. J. Comp. Neurol. 395, 535-547 (1998). (Pubitemid 28226097)
82. Morimoto, T. et al. Involvement of the histaminergic system in leptin-induced suppression of food intake. Physiol. Behav. 67, 679-683 (1999).
83. Sakata, T. et al. Modulation of neuronal histamine in control of food intake. Physiol. Behav. 44, 539-543 (1988). (Pubitemid 19030115)
84. Dhillon, H. et al. Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis. Neuron 49, 191-203 (2006). (Pubitemid 43089637)
85. Gotoh, K. et al. Glucagon-like peptide-1, corticotropin-releasing hormone, and hypothalamic neuronal histamine interact in the leptin-signaling pathway to regulate feeding behavior. FASEB J. 19, 1131-1133 (2005). (Pubitemid 40946441)
86. Elmquist, J. K., Ahima, R. S., Elias, C. F., Flier, J. S. & Saper, C. B. Leptin activates distinct projections from the dorsomedial and ventromedial hypothalamic nuclei. Proc. Natl Acad. Sci. USA 95, 741-746 (1998). (Pubitemid 28083814)
87. Sakurai, T. & Mieda, M. Connectomics of orexin-producing neurons: interface of systems of emotion, energy homeostasis and arousal. Trends Pharmacol. Sci. 32, 451-462 (2011).
88. Ishizuka, T. et al. A role of the histaminergic system for the control of feeding by orexigenic peptides. Physiol. Behav. 89, 295-300 (2006). (Pubitemid 44462776)
89. Zigman, J. M., Jones, J. E., Lee, C. E., Saper, C. B. & Elmquist, J. K. Expression of ghrelin receptor mRNA in the rat and the mouse brain. J. Comp. Neurol. 494, 528-548 (2006). (Pubitemid 41791000)
90. Nishino, S. et al. Decreased CSF histamine in narcolepsy with and without low CSF hypocretin-1 in comparison to healthy controls. Sleep 32, 175-180 (2009).
91. Kanbayashi, T. et al. CSF histamine contents in narcolepsy, idiopathic hypersomnia and obstructive sleep apnea syndrome. Sleep 32, 181-187 (2009).
92. -/- mice and patients. Neurobiol. Dis. 30, 74-83 (2008).
93. Peyron, C. et al. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nature Med. 6, 991-997 (2000).
94. Scammell, T. E. & Mochizuki, T. Is low histamine a fundamental cause of sleepiness in narcolepsy and idiopathic hypersomnia? Sleep 32, 133-134 (2009).
95. 3 receptor antagonists go to clinics. Biol. Pharm. Bull. 31, 2163-2181 (2008).
96. 3 receptor: an attractive target for the treatment of cognitive disorders. Br. J. Pharmacol. 154, 1166-1181 (2008). (Pubitemid 351992052)
97. 3 receptor antagonists: from target identification to drug leads. Biochem. Pharmacol. 73, 1084-1096 (2007). (Pubitemid 46413171)
98. Passani, M. B. & Blandina, P. Histamine receptors in the CNS as targets for therapeutic intervention. Trends Pharmacol. Sci. 32, 242-249 (2011).
99. Tg2576 mouse model of Alzheimer's disease. Neurobiol. Learn. Mem. 95, 64-72 (2011).
100. Varaschin, R. K., Akers, K. G., Rosenberg, M. J., Hamilton, D. A. & Savage, D. D. Effects of the cognition-enhancing agent ABT-239 on fetal ethanol-induced deficits in dentate gyrus synaptic plasticity. J. Pharmacol. Exp. Ther. 334, 191-198 (2010).
101. 3 receptor antagonist, normalizes acetylcholine neurotransmission and has efficacy in translational rat models of cognition. Neuropharmacology 56, 1131-1137 (2009).
102. 3 antagonists for the treatment of cognitive disorders and Alzheimer's disease. J. Pharmacol. Exp. Ther. 336, 38-46 (2011).
103. Welty, N. & Shoblock, J. R. The effects of thioperamide on extracellular levels of glutamate and GABA in the rat prefrontal cortex. Psychopharmacology (Berl.) 207, 433-438 (2009).
104. 3 receptor antagonists reverse delay-dependent deficits in novel object discrimination by enhancing retrieval. Psychopharmacology (Berl.) 202, 141-152 (2009).
105. 1-antagonism in humans: a literature review. Brain Res. Rev. 64, 263-282 (2010).
106. 3 receptor ligands making the final push towards the market? Expert Opin. Investig. Drugs 20, 1629-1648 (2011).
107. Cho, W. et al. Additive effects of a cholinesterase inhibitor and a histamine inverse agonist on scopolamine deficits in humans. Psychopharmacology (Berl.) 218, 513-524 (2011).
108. 3 receptor antagonist for the treatment of adults with attention-deficit hyperactivity disorder. CNS Drugs 26, 421-434 (2012).
109. Rinne, J. O. et al. Increased brain histamine levels in Parkinson's disease but not in multiple system atrophy. J. Neurochem. 81, 954-960 (2002). (Pubitemid 34811944)
110. Nakamura, S. et al. Large neurons in the tuberomammillary nucleus in patients with Parkinson's disease and multiple system atrophy. Neurology 46, 1693-1696 (1996). (Pubitemid 26185795)
111. Nowak, P. et al. Histaminergic activity in a rodent model of Parkinson's disease. Neurotox. Res. 15, 246-251 (2009).
112. 3 receptors in basal ganglia and frontal cortex of healthy controls and patients with Parkinson's disease. Neurobiol. Dis. 8, 707-716 (2001). (Pubitemid 32758674)
113. 3 receptors in the striatum and substantia nigra after 6-hydroxydopamine-induced denervation of dopaminergic neurons: an autoradiographic study. Neurosci. Lett. 178, 19-22 (1994). (Pubitemid 24274351)
114. 3 receptors in the brain of 6-hydroxydopamine-lesioned rats. Eur. J. Neurosci. 12, 3823-3832 (2000).
115. 3 receptor ligands modulate L-dopa-evoked behavioral responses and L-dopa derived extracellular dopamine in dopamine-denervated rat striatum. Neurotox. Res. 13, 231-240 (2008).
116. Sakumoto, T., Sakai, K., Jouvet, M., Kimura, H. & Maeda, T. 5-HT immunoreactive hypothalamic neurons in rat and cat after 5-HTP administration. Brain Res. Bull. 12, 721-733 (1984). (Pubitemid 14073036)
117. Yanovsky, Y. et al. L-Dopa activates histaminergic neurons. J. Physiol. 589, 1349-1366 (2011).
118. 3 receptors depress synaptic transmission in the corticostriatal pathway. Neuropharmacology 40, 106-113 (2001). (Pubitemid 33779805)
119. Gomez-Ramirez, J., Johnston, T. H., Visanji, N. P., Fox, S. H. & Brotchie, J. M. Histamine H3 receptor agonists reduce L-dopa-induced chorea, but not dystonia, in the MPTP-lesioned nonhuman primate model of Parkinson's disease. Mov. Disord. 21, 839-846 (2006). (Pubitemid 44028305)
120. 2 receptor antagonism on levodopa-induced dyskinesia in the MPTP-macaque model of Parkinson's disease. Mov. Disord. 25, 1379-1390 (2010).
121. Schwartz, J. C. The histamine H3 receptor: from discovery to clinical trials with pitolisant. Br. J. Pharmacol. 163, 713-721 (2011).
122. Fernandez, T. V. et al. Rare copy number variants in tourette syndrome disrupt genes in histaminergic pathways and overlap with autism. Biol. Psychiatry 71, 392-402 (2012).
123. Kalanithi, P. S. et al. Altered parvalbumin-positive neuron distribution in basal ganglia of individuals with Tourette syndrome. Proc. Natl Acad. Sci. USA 102, 13307-13312 (2005). (Pubitemid 41325019)
124. Kataoka, Y. et al. Decreased number of parvalbumin and cholinergic interneurons in the striatum of individuals with Tourette syndrome. J. Comp. Neurol. 518, 277-291 (2010).
125. Turjanski, N. et al. PET studies of the presynaptic and postsynaptic dopaminergic system in Tourette's syndrome. J. Neurol. Neurosurg. Psychiatry 57, 688-692 (1994). (Pubitemid 24182952)
126. Singer, H. S. et al. Elevated intrasynaptic dopamine release in Tourette's syndrome measured by PET. Am. J. Psychiatry 159, 1329-1336 (2002). (Pubitemid 34832714)
127. Humbert-Claude, M., Davenas, E., Gbahou, F., Vincent, L. & Arrang, J. M. Involvement of histamine receptors in the atypical antipsychotic profile of clozapine: a reassessment in vitro and in vivo. Psychopharmacology (Berl.) 220, 225-241 (2012).
128. Prell, G. D. et al. Histamine metabolites in cerebrospinal fluid of patients with chronic schizophrenia: their relationships to levels of other aminergic transmitters and ratings of symptoms. Schizophr. Res. 14, 93-104 (1995).
129. 3 receptor radioligand binding in post-mortem brain samples from subjects with psychiatric diseases. B r. J. Pharmacol. 157, 118-129 (2009).
130. 1 receptors in schizophrenic patients measured by positron emission tomography. Eur. Neuropsychopharmacol. 15, 185-191 (2005). (Pubitemid 40193424)
131. Kaminsky, R., Moriarty, T. M., Bodine, J., Wolf, D. E. & Davidson, M. Effect of famotidine on deficit symptoms of schizophrenia. Lancet 335, 1351-1352 (1990). (Pubitemid 20186429)
132. Rosse, R. B. et al. An open-label study of the therapeutic efficacy of high-dose famotidine adjuvant pharmacotherapy in schizophrenia: preliminary evidence for treatment efficacy. Clin. Neuropharmacol. 19, 341-348 (1996). (Pubitemid 26250117)
133. Martinez, M. C. Famotidine in the management of schizophrenia. Ann. Pharmacother. 33, 742-747 (1999). (Pubitemid 29309735)
134. 2 receptors as a novel approach to treat schizophrenia: a double-blind, randomized clinical trial. J. Clin. Psychopharmacol. (in the press).
135. Arrang, J. M. Histamine and schizophrenia. Int. Rev. Neurobiol. 78, 247-287 (2007).
136. Wagner, U., Segura-Torres, P., Weiler, T. & Huston, J. P. The tuberomammillary nucleus region as a reinforcement inhibiting substrate: facilitation of ipsihypothalamic self-stimulation by unilateral ibotenic acid lesions. Brain Res. 613, 269-274 (1993). (Pubitemid 23179978)
137. Wagner, U., Weiler, H. T. & Huston, J. P. Amplification of rewarding hypothalamic stimulation following a unilateral lesion in the region of the tuberomammillary nucleus. Neuroscience 52, 927-932 (1993). (Pubitemid 23063535)
138. Huston, J. P., Wagner, U. & Hasenohrl, R. U. The tuberomammillary nucleus projections in the control of learning, memory and reinforcement processes: evidence for an inhibitory role. Behav. Brain Res. 83, 97-105 (1997). (Pubitemid 27086621)
139. Brabant, C. et al. The psychostimulant and rewarding effects of cocaine in histidine decarboxylase knockout mice do not support the hypothesis of an inhibitory function of histamine on reward. Psychopharmacology (Berl.) 190, 251-263 (2007). (Pubitemid 46011185)
140. 3 receptor mechanisms. FASEB J. 15, 1074-1076 (2001).
141. Nuutinen, S. et al. Evidence for the role of histamine H3 receptor in alcohol consumption and alcohol reward in mice. Neuropsychopharmacology 36, 2030-2040 (2011).
142. Nuutinen, S., Vanhanen, J., Pigni, M. C. & Panula, P. Effects of histamine H3 receptor ligands on the rewarding, stimulant and motor-impairing effects of ethanol in DBA/2J mice. Neuropharmacology 60, 1193-1199 (2011).
143. 3 receptor antagonist, reduces the abuse-related effects of alcohol in rats. Psychopharmacology (Berl.) 214, 829-841 (2011).
144. 3 receptor-dependent mechanisms regulate ethanol stimulation and conditioned place preference in mice. Psychopharmacology (Berl.) 208, 75-86 (2010).
145. Alakarppa, K. et al. Effect of alcohol abuse on human brain histamine and tele-methylhistamine. Inflamm. Res. 51, S40-S41 (2002). (Pubitemid 34298989)
146. Fogel, W. A. et al. Neuronal storage of histamine in the brain and tele-methylimidazoleacetic acid excretion in portocaval shunted rats. J. Neurochem. 80, 375-382 (2002). (Pubitemid 36383021)
147. 3 receptor sites in autopsied brain tissue from cirrhotic patients who died in hepatic coma. J. Hepatol. 39, 522-527 (2003). (Pubitemid 37204651)
148. Suzuki, T., Takamori, K., Misawa, M. & Onodera, K. Effects of the histaminergic system on the morphine-induced conditioned place preference in mice. Brain Res. 675, 195-202 (1995).
149. Gong, Y. X., Zhang, W. P., Shou, W. T., Zhong, K. & Chen, Z. Morphine induces conditioned place preference behavior in histidine decarboxylase knockout mice. Neurosci. Lett. 468, 115-119 (2010).
150. 3 receptor antagonist thioperamide in rats. Eur. J. Pharmacol. 363, 93-101 (1998). (Pubitemid 29057751)
151. Munzar, P., Tanda, G., Justinova, Z. & Goldberg, S. R. Histamine H3 receptor antagonists potentiate methamphetamine self-administration and methamphetamine-induced accumbal dopamine release. Neuropsychopharmacology 29, 705-717 (2004). (Pubitemid 38402478)
152. Brabant, C., Charlier, Y., Quertemont, E. & Tirelli, E. The H3 antagonist thioperamide reveals conditioned preference for a context associated with an inactive small dose of cocaine in C57BL/6J mice. Behav. Brain Res. 160, 161-168 (2005).
153. Handel, A. E., Giovannoni, G., Ebers, G. C. & Ramagopalan, S. V. Environmental factors and their timing in adult-onset multiple sclerosis. Nature Rev. Neurol. 6, 156-166 (2010).
154. Tuomisto, L., Kilpelainen, H. & Riekkinen, P. Histamine and histamine-N-methyltransferase in the CSF of patients with multiple sclerosis. Agents Actions 13, 255-257 (1983).
155. Lock, C. et al. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nature Med. 8, 500-508 (2002). (Pubitemid 34546753)
156. Logothetis, L. et al. A pilot, open label, clinical trial using
157. Alonso, A., Jick, S. S. & Hernan, M. A. Allergy, histamine 1 receptor blockers, and the risk of multiple sclerosis. Neurology 66, 572-575 (2006). (Pubitemid 43739890)
158. Dimitriadou, V., Pang, X. & Theoharides, T. C. Hydroxyzine inhibits experimental allergic encephalomyelitis (EAE) and associated brain mast cell activation. Int. J. Immunopharmacol. 22, 673-684 (2000). (Pubitemid 30407021)
159. 1. Science 297, 620-623 (2002). (Pubitemid 34815349)
160. Passani, M. B. & Ballerini, C. Histamine and neuroinflammation: insights from murine experimental autoimmune encephalomyelitis. Front. Syst. Neurosci. 6, 32 (2012).
161. 2 receptor knockout mice is due to dysregulation of cytokine production by antigen-presenting cells. Am. J. Pathol. 164, 883-892 (2004). (Pubitemid 38235470)
162. 3 receptor signaling negatively regulates susceptibility to autoimmune inflammatory disease of the CNS. Proc. Natl Acad. Sci. USA 104, 10146-10151 (2007). (Pubitemid 47175277)
163. 4 receptor optimizes T regulatory cell frequency and facilitates anti-inflammatory responses within the central nervous system. J. Immunol. 188, 541-547 (2012).
164. Musio, S. et al. A key regulatory role for histamine in experimental autoimmune encephalomyelitis: disease exacerbation in histidine decarboxylase-deficient mice. J. Immunol. 176, 17-26 (2006). (Pubitemid 43023244)
165. 3 receptor in the developing CNS and brown fat suggests novel roles for histamine. Mol. Cell. Neurosci. 24, 614-622 (2003). (Pubitemid 37506006)
166. Kinnunen, A., Lintunen, M., Karlstedt, K., Fukui, H. & Panula, P. In situ detection of H1-receptor mRNA and absence of apoptosis in the transient histamine system of the embryonic rat brain. J. Comp. Neurol. 394, 127-137 (1998). (Pubitemid 28173266)
167. 2 receptor in adult and developing rat brain. Neuroscience 102, 201-208 (2001). (Pubitemid 32171867)
168. Prat, A. & Antel, J. Pathogenesis of multiple sclerosis. Curr. Opin. Neurol. 18, 225-230 (2005). (Pubitemid 40813747)
169. 1 receptor complex with doxepin. Nature 475, 65-70 (2011).
170. 1 receptor. J. Med. Chem. 54, 8195-8206 (2011).
171. Auvinen, S. & Panula, P. Development of histamine-immunoreactive neurons in the rat brain. J. Comp. Neurol. 276, 289-303 (1988).
172. Vanhala, A., Yamatodani, A. & Panula, P. Distribution of histamine-, 5-hydroxytryptamine-, and tyrosine hydroxylase-immunoreactive neurons and nerve fibers in developing rat brain. J. Comp. Neurol. 347, 101-114 (1994). (Pubitemid 24262233)
173. Reiner, P. B., Semba, K., Fibiger, H. C. & McGeer, E. G. Ontogeny of histidine-decarboxylase-immunoreactive neurons in the tuberomammillary nucleus of the rat hypothalamus: time of origin and development of transmitter phenotype. J. Comp. Neurol. 276, 304-311 (1988).
174. Molina-Hernandez, A. & Velasco, I. Histamine induces neural stem cell proliferation and neuronal differentiation by activation of distinct histamine receptors. J. Neurochem. 106, 706-717 (2008).
175. Kinnunen, A. & Panula, P. Histamine and tyrosine hydroxylase in developing rat brain. Agents Actions 33, 108-111 (1991).
176. Vincent, S. R., Hokfelt, T., Skirboll, L. R. & Wu, J. Y. Hypothalamic γ-aminobutyric acid neurons project to the neocortex. Science 220, 1309-1311 (1983). (Pubitemid 13104199)
177. Trueta, C. & De-Miguel, F. F. Extrasynaptic exocytosis and its mechanisms: a source of molecules mediating volume transmission in the nervous system. Front. Physiol. 3, 319 (2012).
178. Airaksinen, M. S., Alanen, S., Szabat, E., Visser, T. J. & Panula, P. Multiple neurotransmitters in the tuberomammillary nucleus: comparison of rat, mouse, and guinea pig. J. Comp. Neurol. 323, 103-116 (1992).
179. Sundvik, M. & Panula, P. The organization of the histaminergic system in adult zebrafish (Danio rerio) brain: neuron number, location and co-transmitters. J. Comp. Neurol. 520, 3827-3845 (2012).
180. Trottier, S. et al. Co-localization of histamine with GABA but not with galanin in the human tuberomamillary nucleus. Brain Res. 939, 52-64 (2002). (Pubitemid 34518589)
181. 3 receptor antagonist, attenuates stimulant-induced locomotor activity in the mouse. Eur. J. Pharmacol. 259, 107-114 (1994). (Pubitemid 24207201)
182. 3 receptor. J. Pharmacol. Exp. Ther. 300, 621-628 (2002).
183. 3-receptor inverse agonist thioperamide on the psychomotor effects induced by acutely and repeatedly given cocaine in C57BL/6J mice. Pharmacol. Biochem. Behav. 83, 561-569 (2006). (Pubitemid 43817127)
184. 3-receptor antagonist/inverse agonist, potentiates neurochemical and behavioral effects of haloperidol in the rat. J. Neurosci. 22, 7272-7280 (2002). (Pubitemid 35379181)
185. 3 receptor inverse agonist thioperamide on cocaine-induced locomotion in mice: role of the histaminergic system and potential pharmacokinetic interactions. Psychopharmacology (Berl.) 202, 673-687 (2009).
186. 3 receptor. J. Neurochem. 103, 248-258 (2007). (Pubitemid 47404216)
187. 1 receptor-induced cAMP accumulation in rat striatal slices. Neurosci. Lett. 364, 179-184 (2004). (Pubitemid 38757928)
188. 3-receptor antagonist/inverse agonist, modulates the effects of methamphetamine on neuropeptide mRNA expression in rat striatum. Eur. J. Neurosci. 17, 307-314 (2003). (Pubitemid 36459510)
189. 3 receptors. Br. J. Pharmacol. 157, 64-75 (2009).
190. 3 receptor heteromers provide a selective link to MAPK signaling in GABAergic neurons of the direct striatal pathway. J. Biol. Chem. 286, 5846-5854 (2011).
191. Jin, C. Y. & Panula, P. The laminar histamine receptor system in human prefrontal cortex suggests multiple levels of histaminergic regulation. Neuroscience 132, 137-149 (2005). (Pubitemid 40380721)
192. Jin, C. Y., Kalimo, H. & Panula, P. The histaminergic system in human thalamus: correlation of innervation to receptor expression. Eur. J. Neurosci. 15, 1125-1138 (2002). (Pubitemid 35463614)
193. 3 receptors in the rat thalamus and their modulation after systemic kainic acid administration. Exp. Neurol. 194, 43-56 (2005). (Pubitemid 40723608)
194. Panula, P., Airaksinen, M. S., Pirvola, U. & Kotilainen, E. A histamine-containing neuronal system in human brain. Neuroscience 34, 127-132 (1990). (Pubitemid 20097900)
195. Karlstedt, K., Jin, C. & Panula, P. Expression of histamine receptor Hrh3 and Hrh4 in rat brain endothelial cells. Br. J. Pharmacol. 14 Mar 2013 (doi:10.1111/bph.12173).
196. 2 receptor mRNA levels by dexamethasone in cerebral endothelial cells. J. Cereb. Blood Flow Metab. 19, 321-330 (1999). (Pubitemid 30026922)
197. 4 receptors in allergic inflammation: the search for new antihistamines. Nature Rev. Drug Discov. 7, 41-53 (2008).
198. Ariyasu, H. et al. Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J. Clin. Endocrinol. Metab. 86, 4753-4758 (2001). (Pubitemid 33020516)
199. Tschop, M., Smiley, D. L. & Heiman, M. L. Ghrelin induces adiposity in rodents. Nature 407, 908-913 (2000).
200. 1 receptor: a novel therapeutic target for disrupting diurnal feeding rhythm and obesity. Trends Pharmacol. Sci. 27, 279-284 (2006).
201. 1-receptor mRNA in the rat brain: correlation to L-histidine decarboxylase expression and local upregulation in limbic seizures. Eur. J. Neurosci. 10, 2287-2301 (1998). (Pubitemid 28302331)
202. 1 receptor in the regulation of feeding rhythm and obesity. Diabetes 53, 2250-2260 (2004). (Pubitemid 39145578)
203. Morimoto, T., Yamamoto, Y. & Yamatodani, A. Leptin facilitates histamine release from the hypothalamus in rats. Brain Res. 868, 367-369 (2000). (Pubitemid 30347535)
204. Ericson, H., Blomqvist, A. & Kohler, C. Brainstem afferents to the tuberomammillary nucleus in the rat brain with special reference to monoaminergic innervation. J. Comp. Neurol. 281, 169-192 (1989). (Pubitemid 19091438)