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. Author manuscript; available in PMC: 2022 Jul 20.
Published in final edited form as: Mol Psychiatry. 2022 Jan 20;27(3):1515–1526. doi: 10.1038/s41380-021-01424-3

Figure 5. Reversal of EAAT3 overexpression in adulthood rescues AMPH-induced locomotion and stereotypic behavior and dopaminergic neuron activity.

Figure 5.

(A) Behavior timeline. For all behavioral panels, n = 11 controls, 10 Th-OEs. Developmentally overexpressing Th-OE mice showed increased locomotor activation at low (B) and moderate (D) doses of AMPH and increased stereotypic behavior at 8.0 mg/kg AMPH dose (F). Following doxycycline administration to these same mice, Th-OE mice showed (C) reduced locomotor activation in response to low AMPH dose in comparison with control mice. (E) Locomotor activation of rescue Th-OE mice was indistinguishable from control mice at the moderate AMPH dose. (G) Further, adult-specific rescue Th-OE mice showed AMPH-induced stereotypic behavior that was comparable to the control group. (H) Single-unit recordings timeline. (I) Representative dopaminergic neuron waveform and spiking patterns from naïve adult-specific rescue Th-OE and control animals. For all ephys panels, n = 55 cells/ 6 control mice, 46 cells/ 6 Th-OE mice. (J) Normalized ISI histograms showing no changes in proportion of short duration ISIs in adult-specific rescue Th-OE mice. (K) % spikes fired in bursts, (L) spikes per burst, (M) burst set rate, (N) average burst ISI, (O) average before-burst ISI, and (P) firing rate are not altered in adult-specific rescue Th-OE mice in comparison to control mice. ****P < 0.0001; ***P < 0.001; **P < 0.01; nsP, not significant. Also see Supplementary Figures S8, S9 for naïve adult-specific rescue behavioral experiments.