Long-term potentiation at excitatory amino acid synapses on midbrain dopamine neurons

Evidence suggests that a process analogous to long-term potentiation (LTP) may underlie the enhanced behavioural responses attending chronic administration of amphetamine and cocaine in animals (behavioural sensitization). Augmented excitatory amino acid (EAA)-mediated transmission at the level of midbrain dopamine neurons has been implicated as a change critical to the development of sensitization. Here we provide an initial demonstration that EAA synapses on dopamine neurons can undergo plasticity. Tetanic stimulation of the subthalamic nucleus induced a long-lasting increase (39.2 ± 10.4%) in the amplitude of excitatory post-synaptic potentials recorded in dopamine neurons of the substantia nigra. This LTP, which did not occur in the presence of NMDA antagonists, may constitute the mechanism that lies at the heart of sensitization.