Dopamine “Ups and Downs” in Addiction Revisited

Drugs of abuse can change dopamine (DA) function during the development of addiction. But in what direction? By one view, drug use blunts DA neurotransmission, producing a hypodopaminergic state, and drug use is motivated to overcome DA deficiency. Another view is that drug use enhances DA neurotransmission, producing a sensitized, hyperdopaminergic reaction to drugs and drug cues, and continued drug use is motivated by sensitization of drug ‘wanting’. Here we discuss recent studies using intermittent cocaine self-administration procedures that mimic human patterns of use. These studies support the view that addiction-like behaviour involves sensitized DA responses to drugs and drug cues, consistent with human neuroimaging studies. These results have implications for modeling addiction in the laboratory, and for treatment.