Evidence for the differential co-localization of neurokinin-1 receptors with 5-HT receptor subtypes in rat forebrain

Abstract

Studies suggest that like selective 5-hydroxytryptamine (5-HT; serotonin) reuptake inhibitors, antagonists at neurokinin-1 receptors (NK₁Rs) may have antidepressant and anxiolytic properties. NK₁Rs are present in 5-HT innervated forebrain regions which may provide a common point of interaction between these two transmitter systems. This study aimed to investigate for cellular co-localization between NK₁Rs and 5-HT receptor subtypes in mood-related brain regions in the rat forebrain. With experiments using fluorescence immunocytochemistry, double-labelling methods demonstrated a high degree of co-localization between NK₁Rs and 5-HT_1A receptors in most regions examined. Co-localization was highest in the medial septum (88% NK₁R expressing cells were 5-HT_1A receptor-positive) and hippocampal regions (e.g. dentate gyrus, 65%), followed by the lateral/basolateral amygdala (35%) and medial prefrontal cortex (31%). In contrast, co-localization between NK₁Rs and 5-HT_2A receptors was infrequent (< 8%) in most areas examined except for the hippocampus (e.g. CA3, 43%). Overall co-localization between NK₁Rs and 5-HT_1A receptors was much greater than that between NK₁Rs and 5-HT_2A receptors. Thus, these experiments demonstrate a high degree of co-localization between NK₁Rs and 5-HT_1A receptors in cortical and limbic regions of the rat forebrain. These findings suggest a novel site of interaction between NK₁R antagonists and the 5-HT system.