Neurotransmitter transporters as molecular targets for addictive drugs

• Published in: Drug and alcohol dependence Vol. 51; no. 1; pp. 87 - 96
• Main Authors: Amara, Susan G., Sonders, Mark S.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.06.1998
• Subjects: Amphetamines - pharmacology; Animals; Biogenic Monoamines - metabolism; Carrier Proteins - chemistry; Carrier Proteins - drug effects; Carrier Proteins - genetics; Carrier Proteins - metabolism; Central Nervous System Stimulants - pharmacology; Cocaine - pharmacology; Dopamine - metabolism; Drug addiction; Humans; Ion Transport - physiology; Membrane Potentials - physiology; Membrane Proteins - chemistry; Membrane Proteins - drug effects; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Knockout; Narcotics - pharmacology; Neurobiological aspects; Neurotransmitters; Serotonin - metabolism; Street Drugs - pharmacology; Structure-Activity Relationship; Synaptic Membranes; Synaptic Vesicles - drug effects; GAT1, rat γ-aminobutyric acid transporter 1; DA, dopamine; DAT, dopamine transporter; NET, norepinephrine transporter; GABA, γ-aminobutyric acid; SERT, serotonin transporter; RTI-82, 3β-( p-chlorophenyl)tropane-2β-carboxylic acid, 4′-azido-3′-iodophenylethyl ester; VMAT, vesicular monoamine transporter; VGAT, vesicular γ-aminobutyric acid transporter; VAChT, vesicular acetylcholine transporter; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; MPP +, 1-methyl-4-phenylpyridinium; TM, transmembrane domain; CFT, (−)-2-β-carbomethoxy-3-β-(4-fluorophenyl)tropane; 5-HT, serotonin, 5-hydroxytryptamine; DEEP, 1-[2-(diphenylmethoxy)-ethyl]-4-[2-(4-azido-3-iodophenyl)ethyl]-piperazine
• ISSN: 0376-8716; 1879-0046
• DOI: 10.1016/S0376-8716(98)00068-4

The neurotransmitter dopamine lies at or near the center of current theories of drug abuse and dependence. Multiple lines of evidence indicate that dopaminergic cells play key roles in a variety of motivated behaviors. Accordingly, it is not surprising that cocaine and amphetamines--some of the most widely used illicit drugs--elevate extraneuronal dopamine concentrations through their actions on the plasma membrane dopamine transporter. From the point of view of developing novel pharmacological interventions for the treatment or prevention of psychostimulant abuse, practical benefits may arise from an improved understanding of how neurotransmitter transporters operate and how drugs interact with them.