Addictive drugs primarily act on the neural circuits in the brain that are responsible for activating motivated adaptive behaviours [14, 30]. One important biological pathway is the mesolimbic dopamine system, or the reward pathway, which branches from the dopaminergic neurons of the VTA to the prefrontal cortex (PFC), amygdala, and the NAc [14, 30]. Natural reward pathways in the brain serve to perpetuate evolutionarily beneficial actions such as seeking food or avoiding psychological discomfort, which are referred to as motivated adaptive behaviours [14]. With regards to dependence, the prefrontal cortex is the main regulator of motivation and thus it determines the motivational value and intensity of behavior [31, 32]. When a beneficial stimulus is detected, the limbic system is capable of processing this information and producing a rewarding sensation that allows the organism to learn the adaptive value of the specified behaviour [15]. Individuals that are struggling with drug dependence display dependence-related behaviours that can be attributed to the dysregulation of prefrontal cortical activity. The transition from voluntary to habitual (and eventually compulsive) opioid use is hypothesized to represent a
