Modulation of brain stem monoamines and gamma-aminobutyric acid by NK1 receptors in rats.

To understand the role of substance P in stress, anxiety and depression, we have investigated in rats the relationship between NK1 receptors and monoamines or GABA, and between substance P and serotonin (5-HT) in brain stem neurons by immunohistochemical double-staining techniques. In the periaqueductal gray and dorsal raphe nucleus, there was no colocalization between NK1 and 5-HT or between NK1 and tyrosine hydroxylase (a marker for adrenaline and dopamine neurons). However, many GABA-positive neurons (> 50%) were NK1 positive, and some substance P-positive neurons were 5-HT positive as well. Almost all locus coeruleus noradrenaline neurons were NK1 positive. Therefore, substance P may promote stress by activating noradrenaline neurons directly and inhibiting 5-HT neurons indirectly via GABA neurons.