Fig. 1

Effect of pharmacogenetic activation of D1-receptor-expressing neurons in the medial shell of the nucleus accumbens on tumor growth. a Schematic diagram showing experimental design. The D1-WT or D1-Cre mice were microinjected with hM3Dq into the medial shell of the nucleus accumbens. Two weeks after the microinjection, mice were transplanted by LLC cells and administered repeatedly by CNO (3 mg/kg, i.p., t.i.d.). b Experimental timeline. c, d Confocal images of Alexa 488 hydrazide-stained D1-hM3Dq-mCherry positive neurons (c) or D2-hM4Di-mCherry positive neurons (d). Scale Bar = 10 µm. Current-clamp traces of D1-hM3Dq-positive (c) and D2-hM4Di-positive (d) neurons by CNO treatment in the nucleus accumbens. e Suppression of the increases in tumor volume (e-i, Two-way repeated measures ANOVA with post-hoc Bonferroni test, ^***p < 0.001 vs D1-WT/hM3Dq) and tumor weight (e-ii, Mann–Whitney test, ^**p < 0.01 vs D1-WT/hM3Dq) by concomitant stimulation of D1-receptor-expressing neurons through activation of hM3Dq in the medial shell of the nucleus accumbens of D1-Cre mice following repeated administration of CNO (3 mg/kg, i.p., t.i.d.) in comparison to those of D1-WT mice. f Effects of concomitant inhibition of D2-MSNs through stimulation of hM4Di in the medial shell of the nucleus accumbens of D2-cre mice by repeated administration of CNO (3 mg/kg, i.p., t.i.d.) on tumor volume (f-i) and tumor weight (f-ii) in comparison to those in D2-WT mice. Each point represents the mean ± S.E.M. of 4–6 animals