NAc can be sub-divided into two regions: the core and the shell. Both regions have different input and output projections (Zahm, 2000) and thought to play different roles in reward pathway (Ito et al., 2004). Recent studies have also reported on different dendritic compartments specifically the proximal and distal (Spruston, 2008). Cocaine regulation of dendritic spines can only be observed in thin, highly motile spine (Kasai et al., 2010) which were thought to be relevant to learning (Moser et al., 1994; Dumitriu et al., 2010) and addiction (Shen et al., 2009; LaPlant et al., 2010). Cocaine exposure caused an increase in spine density in the shell region but a decrease in proximal MSNs in the core region which is seen to be far more enduring (Dumitriu et al., 2012). This enduring change in core reciprocates the idea that shell is involved in addiction development while core in the learning of the addiction or long-term potentiation (Di Chiara, 2002; Ito et al., 2004; Meredith et al., 2008). In a study done by Kourrich and Thomas (2009), however, showed an increase in core MSNs and a decrease in shell MSNs raising the possibility that spine regulation may be compensating the changes in MSNs or spine regulation may be causing a homeostatic tuning of MSNs excitability. Few studies showed homeostatic increase in MSNs excitability following spine downregulation (Azdad et al., 2009; Ishikawa et al., 2009; Huang et al., 2011) supporting the latter but the clear association between both processes is still unknown. A possible mechanism behind the selective downregulation of core MSNs could be dopamine since cocaine withdrawal decreases dopamine levels (Parsons et al., 1991; Baker et al., 2003). Further support to this could be from the higher convergence of the dual glutamatergic and dopaminergic pathways in the core (Zahm and Brog, 1992).

Other than that, a study has found that there is also structural plasticity in input regions to the nucleus accumbens. These inputs include the ventral tegmental area (VTA) which is thought to be important for rewarding stimuli, ventral hippocampus (vPHC) for encoding contextual information, basolateral amygdala (BLA) for relaying emotional context and medial prefrontal cortex (mPFC) providing operational value (Nestler, 2004, Russo & Nestler, 2013). There are two types of medium spiny neurons in the nucleus accumbens specifically dopamine receptor-1-expressing (D1-MSN) and dopamine-receptor-2-expressing (D2-MSN) where D1-MSN is responsible for rewarding stimulation compared to aversive in D2-MSN (Lobo et al., 2010). After cocaine exposure, there was an increase in spine density in BLA and vHPC neurons firing to D1-MSN (Barrientos et al., 2018; Russo et al., 2010) and a decrease in spine projection in mPFC. Since BL