FIGURE 5.

Schematic representation of the role of Cav1.2 and Cav1.3 L-type calcium channels (LTCCs) in the persistent nucleus accumbens (NAc) molecular adaptations following extended withdrawal from repeated cocaine exposure. (a) The cocaine-naive dopamine D1-containing NAc neuron expresses AMPA receptors (GluA1/GluA2 tetramers) and Cav1.2 channels on the cell surface. (b) Twenty-one days following withdrawal from repeated cocaine treatment increased phosphorylation of GluA1 at S845 in the NAc (a PKA site) was paralleled by an increase in cell surface GluA1 and GluA2 levels (and higher levels of Cav1.2 mRNA). (c) A cocaine challenge that elicits expression of cocaine psychomotor sensitization involves dopamine D1 receptors and Cav1.2-activated CaMKII that increases GluA1 phosphorylation at S831 and Cav1.2-activated ERK2, which further increases cell surface GluA1 over that seen in b. This long-term adaptation is dependent on Cav1.3 channels and ERK2 in the ventral tegmental area (VTA) during the development of sensitization. (Reprinted with permission from Ref 148. Copyright 2011 Society for Neuroscience)