Fig. 3: Cocaine chemogenetics in LHb neurons suppresses cocaine-seeking.
From: Cocaine chemogenetics blunts drug-seeking by synthetic physiology
a, Schematic of brain reinforcement circuits engineered to produce artificial feedback through cocaine-gated excitatory channels that oppose the natural suppression of LHb activity resulting from elevated dopamine (DA). Blue, dopamine; red, glutamate; green, GABA. DSt, dorsal striatum; NAc, nucleus accumbens. The diagram was created in BioRender. Sternson, S. (2025) https://BioRender.com/wrre5mw. b, Schematic of dose–response curves for drug self-administration and the potential effects of interfering with reinforcement mechanisms. c, Organization of the cocaine self-administration experiment. inf., infusion. d, Left, image of a coronal rat brain section expressing coca-5HT3-IRES-mCherry in the LHb (scale bar, 1 mm). Right, magnified image of the region indicated by the dashed box (scale bar, 200 µm). e,f, Acquisition of food (e; number of pellets per 3 h) and cocaine infusions per 3 h (f; 0.5 mg per kg per infusion) in rats with coca-5HT3 in the LHb (n = 11 rats) and controls (n = 15 rats). g,h, Rats with coca-5HT3 in the LHb (n = 11 rats) showed significantly lower cocaine infusions per 3 h at 0.125 mg per kg and 0.25 mg per kg (g; P = 0.01 and P = 0.04, respectively, Holm–Šidák post hoc comparison) and intake per 3 h at doses that maintain high-effort self-administration compared with the controls (h; n = 15 rats; mixed-effects ANOVA, dose × transgene interaction, P = 0.02). *P < 0.05. Data are mean ± s.e.m.
