Table 1.

Mechanisms by which drugs of abuse increase the dopamine levels in the nucleus accumbens.

Drug	Mechanism
Amphetamines	Substrates of the dopamine transporter. Promote the efflux of dopamine from cytosolic vesicles into the synaptic cleft [26].
Cocaine	Blockage of the dopamine transporter, increasing the levels of dopamine in the synaptic cleft [24,25].
Opioids	Activate µ-opioid receptors on GABAergic interneurons in the ventral tegmental area inhibiting them, which in turn disinhibits dopaminergic neurons that release dopamine in the nucleus accumbens [23].
Ethanol	Acts as a pro-drug through its first metabolite acetaldehyde, which reacts with dopamine to form the tetrahydroisoquinoline adduct salsolinol [27], likely an agonist of the µ-opioid receptor [28,29]. Salsolinol activates opioid receptors on GABAergic interneurons in the ventral tegmental area inhibiting them, which in turn disinhibits dopaminergic neurons that release dopamine in the nucleus accumbens [30].
Cannabinoids	Agonists of CB1 and CB2 receptors. Activate CB1 receptors on GABAergic interneurons in the ventral tegmental area, which in turn disinhibits dopaminergic neurons that release dopamine in the nucleus accumbens [31].
Nicotine	Activate α4β2 or α6β2 nicotinic acetylcholine receptors in mesolimbic dopaminergic neurons [32], which promotes the release of dopamine in the nucleus accumbens [33].