Fig. 2: Chemogenetic inhibition of the SNc DA neurons induces selective nigrostriatal hypodopaminergia.
From: Hypodopaminergic state of the nigrostriatal pathway drives compulsive alcohol use
A–C hM4Di-mCherry and mCherry expression in SNc DA neurons. A TH::Cre rats received bilateral injection of Cre-dependent hM4Di-mCherry or Cre-dependent mCherry virus in the SNc. B Representative images of TH immunostaining and hM4Di-mCherry expression. Scale bar: 250 μm. C Quantification of transgene expression in distal (dSNc), medial SNc (mSNc) and VTA. Three-way ANOVA showed a significant effect of the area [F(2,129) = 158, P < 0.001, η2 = 0.71], but no effect of transgene, treatment or any interaction between these factors [Fs < 1.04, P > 0.36, partial η2 < 0.02]. D–G Extracellular DA concentrations in aDLS and NAc throughout eight 45 min-fractions collected by microdialysis. Data are normalized to baseline. D Design of the microdialysis experiment. E Time course of extracellular DA concentrations in the aDLS of hM4Di rats treated with C21 (orange, n = 7) or NaCl (red, n = 7) and mCherry rats treated with C21 (gray, n = 7) or NaCl (white, n = 10). F Time course of extracellular DA concentrations in the NAc of hM4Di rats treated with C21 (orange, n = 10) or NaCl (red, n = 9) and mCherry rats treated with C21 (gray, n = 4) or NaCl (white, n = 6). In the fraction collected between 90 and 135 minutes after injection (dotted squares), two-way ANOVA found a treatment x transgene interaction in the aDLS [F(1,27) = 8.63, P < 0.01, partial η2 = 0.24], but not in the NAc [F(1,25) = 0.03, P > 0.5, partial η2 = 0.001]. Data are expressed as mean ± SEM. Bonferroni correction post-hoc analysis: **, P < 0.01. C21: compound 21, SNc substantia nigra pars compacta, TH tyrosine hydroxylase, VTA ventral tegmental area.
