A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dopamine not absorbed by the postsynaptic neuron is blocked from re-entering the presynaptic neuron. This results in increased extracellular concentrations of dopamine and increase in dopaminergic neurotransmission. DRIs are used in the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy for their psychostimulant effects, and in the treatment of obesity and binge eating disorder for their appetite suppressant effects. They are sometimes used as antidepressants in the treatment of mood disorders, but their use as antidepressants is limited given that strong DRIs have a high abuse potential and legal restrictions on their use. Lack of dopamine reuptake and the increase in extracellular levels of dopamine have been linked to increased susceptibility to addictive behavior given increase in dopaminergic neurotransmission. The dopaminergic pathways are considered to be strong reward centers. Many DRIs such as cocaine are drugs of abuse due to the rewarding effects evoked by elevated synaptic concentrations of dopamine in the brain. Society and culture History of use Until the 1950s, dopamine was thought to only contribute to the biosynthesis of norepinephrine and epinephrine. It was not until dopamine was found in the brain in similar levels as norepinephrine that the possibility was considered that its biological role might be other than the synthesis of the catecholamines. Pharmacotherapeutic uses The following drugs have DRI action and have been or are used clinically specifically for this property: amineptine, dexmethylphenidate, difemetorex, fencamfamine, lefetamine, levophacetoperane, medifoxamine, mesocarb, methylphenidate, nomifensine, pipradrol, prolintane, and pyrovalerone. The following drugs are or have been used clinically and possess only weak DRI action, which may or may not be clinically-relevant: adrafinil, armodafinil, bupropion, mazindol, modafinil, nefazodone, sertraline, and sibutramine. The following drugs are or have been clinically used but only coincidentally have DRI properties: benzatropine, diphenylpyraline, etybenzatropine, ketamine, nefopam, pethidine (meperidine), and tripelennamine. The following are a selection of some particularly notably abused DRIs: cocaine, ketamine, MDPV, naphyrone, and phencyclidine (PCP). Amphetamines, including amphetamine, methamphetamine, MDMA, cathinone, methcathinone, mephedrone, and methylone, are all DRIs as well, but are distinct in that they also behave, potentially more potently, as dopamine releasing agents (DRAs) (due to Yerkes–Dodson's law, 'more potently stimulated' may not equal more optimally functionally stimulated). There are very distinct differences