Long-term plasticity at excitatory synapses, such as long-term potentiation (LTP) and long-term depression (LTD), have been extensively studied because of their ability to act as powerful bidirectional modulators of neuronal activity, and could represent key cellular phenomena underlying learning processes in a variety of brain regions.
A series of recent studies have highlighted the potential role of LTP and LTD in the mesolimbic system as molecular events underlying behavioral maladaptations to motivational stimuli, eventually leading to substance abuse. The first study to provide evidence that drugs of abuse lead to long-term changes in synaptic strength showed that a single in vivo exposure to cocaine is sufficient to trigger LTP of AMPA receptor (AMPAR)-mediated excitatory inputs onto dopaminergic (DA) cells in the ventral tegmental area (VTA) (Ungless et al, 2001); although subsequent studies have confirmed and extended these initial findings, an understanding of the mechanisms underlying these forms of drug-induced neuroplasticity is still lacking.
