Behavioural sensitization, which is described as a progressively enhanced responsiveness to the administration of opioid agonists, is hypothesized to also be involved in the pathophysiology of dependence [34]. The enhanced dopamine transmission initiates the positive reward aspect of dependence by triggering a shift from a dopamine-based system to a glutamate-based one in the mesolimbic pathway, which causes characteristics such as impaired decision making and impulsivity to emerge [35]. The transition from drug abuse to dependence is also associated with changes in neuroplasticity that guide the learning of conditioned responses, eventually leading to withdrawal symptoms and drug-seeking behaviours [14, 34, 36].
