In situ hybridization analysis of the C57BL/6J mouse also revealed intense prodynorphin mRNA expression in several brain regions including the olfactory tubercle, caudate putamen, central nucleus of the amygdala, paraventricular nucleus of the hypothalamus, and the nucleus of the solitary tract (Lin et al., 2006). Similarly, in situ hybridization analysis of KOR mRNA showed high expression in the claustrum, endopiriform nucleus, thalamus (paraventricular and parafasicular nuclei), hypothalamus (periventricular, preoptic, and ventromedial nuclei), substantia nigra pars compacta, and ventral tegmental area in mice. (DePaoli et al., 1994). A study examining KOR binding density and KOR mRNA expression in the rat brain reported overlap in many brain regions, including the olfactory tubercle, nucleus accumbens, bed nucleus of the stria terminalis, caudate putamen, amygdala, paraventricular nucleus of the hypothalamus, locus coeruleus, and nucleus of the solitary tract (Mansour et al., 1995). As the anatomical distribution of DYN and KOR expression extensively overlays with reward and stress pathways, the endogenous opioid system is well-positioned to influence affective states by altering stress- and reward-related signaling in the brain (Bruchas et al., 2010; Crowley and Kash, 2015; Wee and Koob, 2010).