nAChR-mediated synaptic plasticity. In addition to augmenting transmitter release, drugs of abuse can induce long-lasting plasticity within midbrain DA centers following both acute and chronic drug administration (Gao et al., 2010). In the VTA, drug-evoked NMDA-mediated plasticity may occur in a similar fashion to that seen in the hippocampus and requires activation of pre-synaptic voltage-gated ion channels. Indeed, several drugs of abuse can elicit LTP in VTA excitatory synapses and increase AMPA receptors without changing the number or function of NMDA receptors (Saal et al., 2003; Jin et al., 2011). Activation of nAChRs by nicotine likely influence the persistent potentiation of these excitatory synapses (Jin et al., 2011), however at this time it is unclear if and how nAChRs play a role in ethanol-mediated NMDAR-dependent plasticity.
