Synaptic plasticity and addiction: learning mechanisms gone awry.

Experience-dependent changes in synaptic strength, or synaptic plasticity, may underlie many learning processes. In the reward circuit for example, synaptic plasticity may serve as a cellular substrate for goal-directed behaviors. Addictive drugs, through a surge of dopamine released from neurons of the ventral tegmental area, induce widespread synaptic adaptations within this neuronal circuit. Such drug-evoked synaptic plasticity may constitute an early cellular mechanism eventually causing compulsive drug-seeking behavior in some drug users. In the present review we will discuss how different classes of addictive drugs cause an increase of dopamine release and describe their effects on synapses within the mesolimbic dopamine system. We will emphasize the early synaptic changes in the ventral tegmental area common to all additive drugs and go on to show how these adaptations may reorganize neuronal circuits, eventually leading to behaviors that define addiction.