Effect of genetic modifications in the synaptic dopamine clearance systems on addiction-like behaviour in mice

During the last 15 years, genetically modified mouse lines have proved to be a valuable research tool. This review summarizes research that studied addiction-like behaviour in mice that had a targeted mutation in the genes of the synaptic dopamine removal systems, i.e. in the dopamine transporter (DAT), a vesicular monoamine transporter 2 (VMAT2) or two dopamine-metabolizing enzymes (monoamine oxidase, MAO, mainly MAO-A isoenzyme, and catechol-O-methyltransferase, COMT). Majority of the mice are knockouts but also some knock-in and knock down mouse lines are included. Most studies have explored DAT, and it has been shown to be the critical target in addiction to psychostimulants. Its role in the development of addiction-like behaviour to nicotine, opioids or ethanol is less clear. VMAT2 also seems to be linked to psychostimulant addiction. MAO-A and COMT have a minor role in addiction-like behaviour that is further complicated by a sexual dimorphism.