nAChR-mediated synaptic plasticity. DA has been shown to be a strong modulator of synaptic plasticity in the PFC by fine tuning glutamatergic transmission and facilitating the induction of LTP or LTD (Otani et al., 2003; Matsuda et al., 2006). Systemic and local administration of nicotine will enhance DA overflow in the medial PFC of rodents (Nisell et al., 1996; Marshall et al., 1997) and both β2-containing and α7 nAChRs influence this response (Table 1) (Livingstone et al., 2009). In rat PFC slices, DA acting through D1 and D2 receptors consistently resulted in LTD and required postsynaptic depolarization and Ca2+ influx, but was independent of NMDAR activation (Law-Tho et al., 1995; Otani et al., 1998). In contrast, in vivo stimulation of the VTA (250 Hz) induced LTP in hippocampo-PFC projections through cooperative actions of D1 and NMDA receptors (Gurden et al., 1999, 2000).
