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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 4. Overexpression of EAAT3 during development is necessary for increased AMPH-induced locomotion and stereotypic behavior in Slc1a1-Th-OE mice.

Figure 4.

(A-F) Life-time rescue experiments. (B) qRT-PCR showing complete rescue of Slc1a1 mRNA expression in Th-OE mice (n = 4 per genotype). For all life-time rescue behavior panels, n = 8 controls, 9 Th-OEs. (C) Life-time rescue Th-OE mice display novelty-induced locomotion that is indistinguishable from littermate controls. (D) Life-time rescue Th-OE mice show a slightly increased locomotor response to a low dose of AMPH via curve-fit analysis; however, no genotype differences are observed in AUC analysis (D, inset). (E) Locomotor response of life-time rescue Th-OE mice to a moderate AMPH dose (AUC, 2-way RM ANOVA; drug × genotype interaction, F (1, 15) = 0.2081, P = 0.6548; drug, F (1, 15) = 18.74, P = 0.0006, genotype, F (1, 15) = 0.3003, P = 0.5917) is indistinguishable from littermate controls. (F) Stereotypic activity at the high AMPH dose in life-time rescue Th-OE mice does not differ from controls. (G-L) Life-time overexpression experiments. (H) qRT-PCR showing increased Slc1a1 mRNA expression in Th-OE mice (n = 4 per genotype). For all life-time overexpression behavior panels, n = 12 controls, 10 Th-OEs. (I) Life-time overexpressing Th-OE mice show increased novelty-induced locomotion. (J-K) Life-time overexpressing Th-OE mice show increased locomotor activation at (J) low (AUC, 2-way RM ANOVA; drug × genotype interaction, F (1, 20) = 4.446, P = 0.0478; drug, F (1, 20) = 23.90, P < 0.0001, genotype, F (1, 20) = 5.347, P = 0.0315), and (K) moderate (AUC, 2-way RM ANOVA; drug × genotype interaction, F (1, 20) = 4.915, P = 0.0384; drug, F (1, 20) = 24.34, P < 0.0001, genotype, F (1, 20) = 5.997, P = 0.0237) doses of AMPH. (L) Stereotypic behavior at 8.0 mg/kg AMPH dose is elevated in Th-OE mice. (M-R) Adult-specific overexpression experiments. (N) qRT-PCR showing increased Slc1a1 expression in Th-OE mice (n = 4 per genotype). For all adult-specific overexpression behavior panels, n = 13 controls, 12 Th-OEs. (O) Adult-specific overexpressing Th-OE mice show novelty-induced locomotor behavior that is indistinguishable from littermate control mice. (P-Q) Locomotor responses in Th-OE mice to (P) low (AUC, 2-way RM ANOVA; drug × genotype interaction, F (1, 23) = 0.3956, P = 0.5356; drug, F (1, 23) = 18.19, P = 0.0003, genotype, F (1, 23) = 0.6658, P = 0.4229), and (Q) moderate (AUC, 2-way RM ANOVA; drug × genotype interaction, F (1, 23) = 0.06689, P = 0.7982; drug, F (1, 23) = 19.62, P = 0.0002, genotype, F (1, 23) = 0.07915, P = 0.7810) doses of AMPH are comparable to control group responses. (R) No genotype differences are observed in AMPH-induced stereotypic behavior in adult-specific overexpressing mice. ****P < 0.0001; **P < 0.01; *P < 0.05; nsP, not significant. Also see Supplementary Figure S7 for anxiety-like measures.