TY - JOUR T1 - Regional Differential Effects of the Novel Histamine H<sub>3</sub> Receptor Antagonist 6-[(3-Cyclobutyl-2,3,4,5-tetrahydro-1<em>H</em>-3-benzazepin-7-yl)oxy]-<em>N</em>-methyl-3-pyridinecarboxamide hydrochloride (GSK189254) on Histamine Release in the Central Nervous System of Freely Moving Rats JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 164 LP - 172 DO - 10.1124/jpet.109.158444 VL - 332 IS - 1 AU - Patrizia Giannoni AU - Andrew D. Medhurst AU - Maria Beatrice Passani AU - Maria Grazia Giovannini AU - Chiara Ballini AU - Laura Della Corte AU - Patrizio Blandina Y1 - 2010/01/01 UR - http://jpet.aspetjournals.org/content/332/1/164.abstract N2 - After oral administration, the nonimidazole histamine H3 receptor antagonist, 6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide hydrochloride (GSK189254), increased histamine release from the tuberomammillary nucleus, where all histaminergic somata are localized, and from where their axons project to the entire brain. To further understand functional histaminergic circuitry in the brain, dual-probe microdialysis was used to pharmacologically block H3 receptors in the tuberomammillary nucleus, and monitor histamine release in projection areas. Perfusion of the tuberomammillary nucleus with GSK189254 increased histamine release from the tuberomammillary nucleus, nucleus basalis magnocellularis, and cortex, but not from the striatum or nucleus accumbens. Cortical acetylcholine (ACh) release was also increased, but striatal dopamine release was not affected. When administered locally, GSK189254 increased histamine release from the nucleus basalis magnocellularis, but not from the striatum. Thus, defined by their sensitivity to GSK189254, histaminergic neurons establish distinct pathways according to their terminal projections, and can differentially modulate neurotransmitter release in a brain region-specific manner. Consistent with its effects on cortical ACh release, systemic administration of GSK189254 antagonized the amnesic effects of scopolamine in the rat object recognition test, a cognition paradigm with important cortical components.© 2010 by The American Society for Pharmacology and Experimental Therapeutics ER -