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.This article is part of a Special Issue entitled ‘Synaptic Plasticity and Addiction’.

► Addictive drugs increase dopamine through three distinct cellular mechanisms. ► Mesolimbic dopamine causes drug-evoked synaptic plasticity in the VTA. ► In glutamatergic synapses of the VTA, drugs redistribute AMPA and NMDA receptors. ► Drugs alter the rules of activity-dependent plasticity thus reorganizing neural circuits. ► With repetitive drug exposure, adaptations spread beyond the VTA, changing behavior.