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https://www.selleckchem.com/products/tapi-1.html Immunohistochemical analysis showed expression of Cre recombinase in the TMN of cKO mice. The reduction of histamine contents with the decreased Hdc expression in cKO brain was also confirmed. Behavioural studies revealed that chronic histamine depletion in cKO mice induced depression-like behaviour, decreased locomotor activity in the home cage, and impaired aversive memory. Sleep analysis showed that cKO mice exhibited a decrease in wakefulness and increase in non-rapid eye movement sleep throughout the day. Taken together, this study clearly demonstrates that chronic histamine depletion in the adult mouse brain plays a causative role in brain dysfunction.Since our review of central 5-HT receptors and their function twenty years ago, no new 5-HT receptors have been discovered and there is little evidence that this situation will change in the near future. Nevertheless, over this time significant progress has been made in our understanding of the properties of these receptors and in the clinical translation of this information, and some of these developments are highlighted herein. Such highlights include extensive mapping of 5-HT receptors in both animal and human brain, culminating in readily-accessible brain atlases of 5-HT receptor distribution, as well as emerging data on how 5-HT receptors are distributed within complex neural circuits. Also, a range of important pharmacological and genetic tools have been developed that allow selective 5-HT receptor manipulation, in cells through to whole organism models. Moreover, unexpected complexity in 5-HT receptor function has been identified including agonist-dependent signalling that goes beyond the pharmacology of canonical 5-HT receptor signalling pathways set down in the 1980s and 1990s. This new knowledge of 5-HT signalling has been extended by the discovery of combined signalling of 5-HT and co-released neurotransmitters, especially glutamate. Another important ad

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