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, MannWhitney test, unpaired, ** p<0.01, *** p<0.001. (B) AAV-mediated Cre expression in the SN of PMAT fl/fl mice (n=24-25 per group) and WT mice (n=6 per group) did not modify anxiety level in the light dark box). (C) AAV-mediated Cre expression in the SN of PMAT fl/fl and WT mice disrupted locomotor sensitization to cocaine (10 mg/kg). Two-way analysis of variance (ANOVA), High thigmotaxis and impaired response to cocaine induced by AAV-mediated Cre expression in the SN of mice. (A)

, 0007) for PMAT fl/fl mice (n=7-8 per group

, 0001) and day of treatment/AAV type interaction

, Over time, Sidak's post-hoc test showed stronger locomotor sensitization for AAV-eGFP-injected mice than for AAV-eGFP-Cre-injected mice (* p<0.05, ** p<0.01*** p<0.001, compared to day 1). Values are given as mean ± s.e.m

, Mann-Whitney test, unpaired, *** p<0.0001. Representative images are shown on the left. Scale bars represent 100 µm. (B) AAV-mediated Cre expression in the SN of PMAT fl/fl mice (n=9 per group) and WT mice (n=6 per group) reduced dopamine transporter (DAT) immunofluorescence in dorsal striata of PMAT fl/fl mice (n=9 SN injections per group) and WT mice (n=6 SN injections per group). Intensity is expressed as percentage of mean values for AAV-eGFP controls. DLS, dorsolateral striatum; DMS, dorsomedial striatum

, AAV-mediated Cre expression in WT mice (n=6 mice per group) increased the number of cells positive for S439 phosphorylated H2AX (A; n=12 SN injections per group) and for K283 acetylated p53 (B; n=8-9 SN injections per group) in the SN of WT mice. Inset in A shows higher magnification of S439 phosphorylated H2AX apoptotic rings in AAV-eGFP-Cre injected mice. Scale bars represent 50 µm. Student's t-test, unpaired, *** p<0.001. (C) AAV-mediated Cre expression did not alter labeling for D175-cleaved caspase 3 (Cas3), in the SN of WT mice (top; (n=6 mice per group), DNA break and programmed cell death markers induced by AAV