Manipulations of the SP/NK1R system have been shown to influence several addiction-related behaviors. For example, NK1R knockout mice do not display morphine conditioned place preference, and self-administer morphine at lower rates. Morphine-induced locomotor activation and psychomotor sensitization are also blunted in these mice (Murtra et al., 2000; Ripley et al., 2002). Reduced morphine self-administration following inactivation of NK1Rs has been localized to the amygdala (Gadd et al., 2003). Reduced opioid reward following NK1R blockade was recently also supported by observations that this treatment attenuates the ability of morphine to lower intracranial self-stimulation thresholds (Robinson et al., 2012). Co-administration of SP and morphine prevents the internalization and acute desensitization of the mu opioid receptor typically induced by morphine, which may account for the involvement of the NK1R in opioid reward (Yu et al., 2009).
