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. Author manuscript; available in PMC: 2014 Jul 1.
Published in final edited form as: Nat Neurosci. 2013 Nov 24;17(1):73–80. doi: 10.1038/nn.3590

Figure 6. Correlations between effects of SYN119 on rectification index (RI), naspm sensitivity, and cue-induced cocaine-seeking.

Figure 6

(a) Timeline (SA, self-administration) and data demonstrating changes in RI (from Fig. 5) following repeated SYN119 treatment. (b) To further assess the contribution of CP-AMPARs to the changes in RI shown in (a), the CP-AMPAR antagonist naspm (100μM) was bath-applied for 15 min and EPSC amplitude was measured at a holding potential of -70mV (EPSC-70mV; data are normalized to pre-naspm baseline; b, left). As expected, naspm decreased EPSC-70mV by ~30% in cocaine rats that received repeated vehicle injections (b, right). In contrast, naspm sensitivity was significantly reduced in rats recorded 2–3 days after the last SYN injection (b, right), a time when the RI was also reduced (panel a and Fig. 5c) and cue-induced cocaine-seeking was below incubated levels (Fig. 5b). By 4–5 days following the last SYN injection, the RI and naspm sensitivity had returned to levels more similar to those observed in cocaine/vehicle (Coc/Veh) animals (a,b), as had cue-induced cocaine-seeking (Fig. 5b). ***p<0.001, **p=0.003, *p=0.04 versus Coc/Veh; Coc/Veh, n=5 cells/2 rats; SYN D2, n=4 cells/2 rats; SYN D3, n=4 cells/2 rats; SYN D4–5, n=6 cells/3 rats. (c) Analyses of correlations between cocaine-seeking (measured as percent change from active hole responses on WD1), RI and naspm sensitivity for all rats shown in Fig. 5b,c. As expected, naspm-sensitivity was highly correlated with RI values (c, left), indicating that an elevated RI is due to enhanced CP-AMPAR-mediated transmission. In addition, cocaine-seeking correlated with both RI and naspm sensitivity (c, middle and right).