Modulation of brain stem monoamines and γ-aminobutyric acid by NKI receptors in rats

To understand the role of substance P in stress, anxiety and depression, we have investigated in rats the relationship between NKI 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 NKI and 5-HT or between NKI and tyrosine hydroxylase (a marker for adrenaline and dopamine neurons). However, many GABA-positive neurons (>50%) were NKI positive, and some substance P-positive neurons were 5-HT positive as well. Almost all locus coeruleus noradrenaline neurons were NKI positive. Therefore, substance P may promote stress by activating noradrenaline neurons directly and inhibiting 5-HT neurons indirectly via GABA neurons.