Fig. 4.
Adult Control mice intra-VTA infused with ZD7288 show RCF behavior and reduced IhcurrentA, pooled data for Forced Swim Test (FST; left), Tail Suspension Test (TST; middle) and Saccharin Preference Test (SPT, right). Control mice intra-VTA infused with ZD7288 (CTRL-ZD) show reduced immobility behavior in both FST (***p < 0.001, t -test = 4.69, 7 CTRL-ZD and 6 CTRL-Veh mice) and TST (*p < 0.05, t -test = 2.7, 7 CTRL-ZD and 6 CTRL-Veh) as well as increased percentage of saccharin intake in comparison with Vehicle-treated animals (CTRL-Veh mice; p < 0.05). B, to the left, I–V curves depicting significant reduction of Ih current density in DA neurons in the iVTA from CTRL-ZD mice compared to CTRL-Veh. Two-way repeated measures ANOVA: in vivo treatment, F(1,31) = 8.58, **p = 0.0063; in vivo treatment x membrane potential, F(3,29) = 7.09, **p = 0.0010; membrane potential, F(3,29) = 48.21, ***p = 2.17 × 10−11. For CTRL-Veh vs CTRL-ZD with Bonferroni's post-hoc analysis: at Vh −60 mV, CTRL-Veh 0 ± 1 pA, CTRL-ZD – 2 ± 1 pA, p = 1; at Vh −80 mV, CTRL-Veh – 37 ± 5 pA, CTRL-ZD – 17 ± 3 pA, p = 1; at Vh −100 mV, CTRL-Veh – 138 ± 15 pA, CTRL-ZD – 76 ± 10 pA, **p = 0.0029; at Vh – 120 mV, CTRL-Veh – 204 ± 23 pA, CTRL-ZD – 137 ± 15 pA, ***p = 8.12 × 10−4 (CTRL-Veh, n = 40; CTRL-ZD, n = 32). To the right, example Ih currents. Scale bars: 200 pA, 0.5 s. C, f – I relationships (left) and typical current-clamp recordings (right) depicting lack of difference in frequency of APs evoked in CTRL-ZD and CTRL-Veh neurons, as revealed by two-way repeated measures ANOVA: treatment, F(1,28) = 3.4, p = 0.075; treatment x IInj F(3,26) = 0.099, p = 0.95; (CTRL-Veh n = 39, CTRL-ZD n = 30). Scale bars: 30 mV, 1 s.