Figure 5. Intra-NAc inhibition of NR2B-containing NMDARs prevented cocaine-induced locomotor sensitization. A, Representative diagram showing the installation sites of intra-NAc mini pumps in Ro256981–cocaine (black), Ro256981–saline (open circle), APV–cocaine (light gray), and APV–saline (dark gray) rats. B, Cocaine-induced locomotor sensitization (tested in cocaine-treated rats) as well as the basal locomotor activity (tested in saline-treated rats) were not affected by the surgical installation of intra-NAc mini pumps. C, Examples showing the inhibition of NMDAR EPSCs by Ro256981 (20 nm) and APV (500 nm). D, Dose–response curve showing a concentration range (20–200 nm) in which Ro256981 exhibited a high affinity inhibition of NMDAR EPSCs. E, Grouped data showing that application of 20 nm Ro256981, but not 500 nm APV, significantly decreased the T1/2 (decay kinetics) of NMDAR EPSCs in NAc MSNs. F, Basal/spontaneous locomotor activity was not affected by chronic intra-NAc perfusion of Ro256981 or APV. G, Control for rapid intra-NAc perfusion. With the identical experimental procedure, intra-NAc perfusion of 1 μm NBQX 15 min before cocaine injection prevented cocaine-induced increase in locomotor responses. H, Grouped data showing that intra-NAc inhibition of NR2B-containing NMDARs (by Ro256981), but not a partial, nonselective inhibition of NAc NMDARs, prevented the development of locomotor sensitization. I, Grouped data showing that intra-NAc inhibition of NR2B-containing NMDARs did not affect the expression of cocaine-induced locomotor sensitization. Numbers in parentheses indicate number of cells or number of rats; *p < 0.05; **p < 0.01. Contl, Control; Ro, Ro256981; Sal, saline; Coc, cocaine.