**2. Neurobiological mechanism**

The development of addiction finds its anatomical and neurobiological bases in the so-called neurocircuitry of reward, and it is important to better understand when and how the reward system is activated [13]. The term "reward" is defined as any event that increases the probability of a response with a positive hedonic component. The ascending meso-cortico-striatal dopamine systems seem to have a key role in the rewarding properties of nearly all drugs of abuse [14]. In humans, positron emission tomography studies have shown that intoxicating doses of alcohol and drugs release dopamine and opioid peptides into the ventral striatum [15, 16], activating low-affinity dopamine D1 receptors, which are necessary for the rewarding effects of drugs [17]. This specific circuitry includes not only dopamine and opioid peptides but also γ-aminobutyric acid (GABA), glutamate, serotonin, acetylcholine and endocannabinoid systems that act at the level of either the ventral tegmental area or nucleus accumbens. Balanced circuits result in proper inhibitory control and decision-making and normal functioning of reward, motivation, stress and memory circuits. These circuits also interact with circuits that are involved in mood regulation, including stress reactivity (which involves the amygdala, hypothalamus and habenula) and interception (which involves the insula and anterior cingulate cortex and contributes to the awareness of negative emotional states). Drugs of abuse usurp executive function circuits, motivational circuits and stress circuits via multiple neurotransmitter-specific neuroplasticity circuits. Key neurotransmitters that are implicated in these neuroadaptations include dopamine, enkephalins, glutamate, γ-aminobutyric acid, norepinephrine, corticotropin-releasing factor (CRF), dynorphin, neuropeptide Y and endocannabinoids.
