Synaptic strengthening can be accompanied by neurite outgrowth, spine splitting, and synaptogenesis. Repeated psychostimulant exposure leads to synaptogenesis in several mesocorticolimbic areas (Li et al., 2004; Pulipparacharuvil et al., 2008; Robinson and Kolb, 1999; Shen et al., 2009) and several molecules have been associated with this process, including the neuronal-activity-regulated pentraxin (Narp). Narp is secreted into the extracellular matrix, concentrates at excitatory complexes, and facilitates AMPAR clustering by forming extracellular, multimeric complexes (O’Brien et al., 1999). Following a single methamphetamine injection, Narp mRNA is upregulated in the dorsal striatum, hippocampus, and some regions of the neocortex (Ujike et al., 2002), although a parallel increase in protein expression was not detectable after either acute or repeated psychostimulant exposure (Lu et al., 2002). However, Narp protein expression in the prefrontal cortex was correlated with the magnitude of spontaneous motoric response to a novel environment (Lu et al., 2002), and heightened reactivity to novel situations has been used as a measure of impulsivity and a putative drug abuse liability indicator (Lu et al., 2002; Stoffel and Cunningham, 2008). Narp knockout decreased cocaine-mediated reinforcement
