The NK1R modulates monoaminergic transmission following stress exposure. During forced-swim stress, NK1R antagonism promotes active coping behavior and prevents the suppression of 5-HT release in the lateral septum that is normally seen under these conditions (Ebner et al., 2008b). SP is released in response to stress, and it has been shown that NK1R activation suppresses dorsal raphe activity and 5-HT release (Guiard et al., 2007; Valentino et al., 2003), and that genetic or pharmacological inhibition of the NK1R can increase serotonergic activity (Conley et al., 2002; Gobbi et al., 2007; Santarelli et al., 2001). In addition, NK1Rs are also present on the noradrenergic cell bodies of the locus coeruleus (Chen et al., 2000; Ma and Bleasdale, 2002), and dynamically regulate the activity of this nucleus. The ability of NK1R to modulate noradrenergic transmission is especially intriguing, as this system is involved in stress-induced reinstatement of drug seeking and escalated self-administration of multiple classes of drugs.
