Histamine excites noradrenergic neurons in locus coeruleus in rats

Histamine is implicated in the control of many brain functions, in particular the control of arousal. Histaminergic neurons send dense projections through the entire brain, including the locus coeruleus (LC) - the main noradrenergic (NAergic) nucleus. In this study, we have examined the effect of bath-applied histamine on cells in the LC by single-unit recordings in slices and the expression of histamine receptors in this area by single-cell RT-PCR. Histamine (10 mu M) increased the firing of NAergic cells to 130 +/- 9% of control, 100 mu M to 256 +/- 58% of control. This excitation was unaffected by blocking synaptic transmission. Histamine-mediated excitation was blocked by an H-1 receptor antagonist, mepyramine, in 78% of cells and by cimetidine, an H-2 receptor antagonist, in 42% of cells, but not by the H-3 receptor antagonist, thioperamide. RT-PCR revealed that mRNA for the H-1 receptor was expressed in 77% of isolated LC neurons, mRNA for the H-2 receptor in 41% of LC neurons and H-3 receptors in 29%. These findings underline the coordination between aminergic systems and suggest that the arousal induced by the histamine system could involve excitation of noradrenergic neurons in the locus coeruleus. (c) 2005 Elsevier Ltd. All rights reserved.