Drugs has been known to induce structural plasticity of dendrites since 1997 (Robinson & Kolb, 2004; Russo et al., 2009; Dietz et al., 2009; Russo et al. 2010). Since then, researches on various drugs of abuse have shown to induce a structural change in the brain’s reward circuitry such as opiates decreasing number of NAc medium spiny neurons (MSN) in contrast to stimulants which increases NAc MSN numbers. Early withdrawal after exposure to chronic cocaine induces expression of N-methyl-D-aspartate (NMDA) glutamate receptors at MSN surface causing silent synapse formation and long-term depression (LTD). Prolonged withdrawal will cause retraction of the NMDA receptors to be replaces by α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) glutamate receptors changing structure of the spine to become mushroom shaped and promoting long-term potentiation (LTP). This change however can be reversed easily by a challenge dose of cocaine (Figure 2) (Russo et al.,2010). Figure 2. Cocaine-induced synaptic and structural plasticity (Russo et al., 2010) At a molecular level, this is caused by regulation of actin cytoskeleton via scaffolding proteins as well as GTPases and they are activated by transcription factor ΔFosB and cyclic AMP response element binding protein (CREB) which induces spinogenesis (Heiman et al., 2008; Kim et al., 2009). On the other hand, ΔFosB also regulates cyclin dependent kinase 5 (Cdk5) (Kumar et al., 2005) as well as nuclear factor κB (NFκB) (Russo et al., 2009) where both molecules play a role in cocaine-induced spine formation showing the major role of ΔFosB in cocaine-induced structural changes. The only paradox here is that both opiates and cocaine induce similar behavioural phenotypes (Russo et al., 2010) as well as drug administration and withdrawal symptoms although they have completely opposite effect on the NAc MSNs. A few possible hypothesises include changes in synaptic plasticity having a bidirectional property where a change in both directions result in similar behavioural phenotypes, decrease in neuronal complexity in one brain area is compensated by a strength>