The toughest challenge for all forms of synaptic plasticity is the demonstration of a causal link between a specific synaptic modification and a specific behavior. Indeed, the specific behavioral role of the original form of long-lasting synaptic plasticity, NMDAR-dependent LTP in the hippocampus, is still not unequivocally demonstrated. Space constraints prevent us from reviewing all the behavioral literature implicating drug-evoked synaptic plasticity in addiction-related behaviors. Instead, we will focus on studies that have used ex vivo approaches to correlate drug-elicited behavioral changes with mechanistic investigations of the underlying synaptic plasticity. The behavioral models mimicking core components of drug addiction that have been studied most extensively in this context are self administration, locomotor sensitization, conditioned place preference (CPP), drug-evoked relapse, cue-induced cocaine seeking and incubation of craving.
