Data suggests repeated administration of a drug causes altered dopaminergic and glutamatergic transmission in the mesocorticolimbic system (Vanderschuren and Kalivas, 2000; Pascual et al., 2009) and is associated with the neuroplastic changes discussed thus far in this review. Up-regulation of receptors may not be the sole cause of drug-induced locomotor sensitization, since the timing of these events don't necessarily correlate, but likely plays a role in the development of this behavioral response (Vezina, 2007). nAChRs are up-regulated in the entire brain after long exposures to nicotine but nAChRs in the VTA and NAc are the most probable regions implicated for the induction of sensitization (Parker et al., 2004). Long-lasting behavioral sensitization has been shown to correlate well with LTP, reflecting persistent adaptations in neural mechanisms such as the modulation of synaptic strengths, change in neurotransmitter release, alterations in gene expression and formation of new connections between synapses. In the next section, we will focus on nicotine and ethanol's effect on behavioral sensitization.
