Mimicking synaptic effects of addictive drugs with selective dopamine neuron stimulation

Abstract

The synaptic changes induced by initial drug exposure leave a trace on neural systems that can eventually manifest in compulsive drug-seeking behavior. A single injection of cocaine has been shown to induce a change in the AMPA receptor (AMPAR) subunit composition at glutamatergic synapses onto ventral tegmental area (VTA) dopamine (DA) neurons. This change is long-lasting (up to months following self-administration) and represents an important functional change at the synaptic level following cocaine use. We recently published findings that cocaine's action at the DA transporter (DAT) is necessary for the induction of AMPAR redistribution and that this can also be mimicked by selective DA neuron stimulation. The stimulation effect is dependent on D1 receptors within the VTA. Furthermore other addictive drugs, although they act through distinct mechanisms, also induce this synaptic change. Here we discuss literature that expands on these observations in an attempt to further clarify the synaptic changes following early drug use.