Figure 4. Dopamine release from striatal presynaptic terminals is restored to WT levels in α4KO/α6L9′S mice. A–F, Hypersensitive α6* nAChR-mediated DA release in α6L9′S OT (A–C) and ST (D–F) is reversed by α4 nAChR subunit deletion. OT or ST from WT, α6L9′S, α4KO, and α4KO/α6L9′S mice was dissected and synaptosomes were prepared. DA release was stimulated with a range of nicotine concentrations (1 nm, 3 nm, 10 nm, 30 nm, 100 nm, 300 nm, 1 μm, 10 μm, 100 μm, 300 μm), and a concentration–response relation for each mouse line is shown for total release (A, D). To determine the relative contribution of α6* and non-α6* receptors, synaptosome samples were incubated with αCtxMII (50 nm). αCtxMII-sensitive (α6* dependent) release is shown in B and E, and α6*-independent release is shown in C and F. G, H, Quantification of DA release measured in A–F for WT, α6L9′S, α4KO, and α4KO/α6L9′S mice in ST and OT. Rmax (G) and EC50 (H) for αCtxMII-sensitive (α6β2*) and αCtxMII-resistant (α4β2*) DA release in ST and OT is shown. Data are expressed as mean ± SEM. The number of mice in each group was as follows: WT, n = 7; α6L9′S, n = 7; α4KO, n = 9; α4KO/α6L9′S, n = 10. All statistically significant comparisons are indicated. *p < 0.05, **p < 0.01, ***p < 0.001.