Fig. 4: Cocaine chemogenetics in LHb neurons suppresses cocaine-induced increases in extracellular dopamine in the NAc.
From: Cocaine chemogenetics blunts drug-seeking by synthetic physiology
a, Schematic showing the stereotaxic delivery of AAV5-Syn::coca-5HT3-IRES-mCherry into the LHb of rats and [18F]fallypride PET procedures. The diagram was created in BioRender. Michaelides, M. (2025) https://BioRender.com/yvwycvv. b, Schematic showing the displacement of [18F]fallypride by cocaine detected using PET. The diagram was created in BioRender. Sternson, S. (2025) https://BioRender.com/9fog7n9. c, Coronal PET brain images co-registered to a magnetic resonance imaging template showing significant cocaine-induced voxel-wise decreases in [18F]fallypride binding in the ventral striatum of control rats (n = 9 rats) and in rats with coca-5HT3 in the LHb (n = 5 rats). d, Time–activity curves of [18F]fallypride binding (standardized uptake value (SUV)) in the ventral striatum (squares) and cerebellum (triangles) calculated as the percentage of the baseline (60–90 min) for control (n = 9 rats, black) and coca-5HT3 (n = 5 rats, red) rats, showing that cocaine selectively displaces [18F]fallypride binding (that is, increases dopamine) in the ventral striatum of control rats (three-way RM-ANOVA, time × transgene × brain region interaction, F25,300 = 3.83, P < 0.001). e, Schematic of the stereotaxic delivery of AAV5-Syn::coca-5HT3-IRES-mCherry and AAV9-Syn::GRABDA and the experimental timeline of fibre photometry procedures. The diagram was created in BioRender. Michaelides, M. (2025) https://BioRender.com/hmnai5g. f, Left, image of a coronal rat brain section showing the optic fibre tract and GRABDA expression (scale bar, 1 mm). Right, magnification of the area indicated on the left (scale bar, 400 µm). g,h, GRABDA response time course with saline and cocaine (5 mg per kg) injection in control rats (g) (n = 5 rats; two-way RM-ANOVA, treatment main effect, F1,5 = 47.77, P = 0.001; time main effect, F2.2,11.1 = 1.84, P = 0.2; treatment × time interaction, F2.1,10.4 = 10.86, P = 0.002) and rats with coca-5HT3 in the LHb (h) (n = 6 rats; two-way RM-ANOVA, treatment main effect, F1,4 = 3.58, P = 0.13; time main effect, F1.5,6.1 = 0.73, P = 0.48; treatment × time interaction, F2.5,10.2 = 2.03, P = 0.17). i, The AUC of time-course measurements with saline- and cocaine-induced (5, 10 and 20 mg per kg) GRABDA responses. Data are mean ± s.e.m.
