Besides anatomical and connectivity differences, there are clear distinctions in DA signaling between the ventral and dorsal striatum which govern their specific brain functions and behavioral output. For example, initial drug use will favor DA release in the NAc shell rather than the dorsolateral striatum (Pontieri et al., 1996; Di Chiara, 2002). Furthermore, these two regions respond differently to stimulus trains that mimic action potentials, with tonic and phasic firing eliciting greater DA release from the dorsolateral striatum and NAc shell, respectively (Zhang et al., 2009). Recently, it was demonstrated that activity-dependent DA transmission in the ventral striatum is mainly controlled by α6*-containing nAChRs (α6α4β2β3 and α6β2*) but in the dorsal striatum non-α6 nAChRs (α4β2 and α4α5β2) are the key players (Exley et al., 2007, 2008, 2011). In summary, DA release in the striatum is modulated by different nAChRs on pre-synaptic DAergic terminals in a frequency-dependent and region-specific manner.
