Figure 7. Treatment with the RXR inhibitor HX531 reduces behavioral responses to cocaine.

(A) Systemic administration of HX531 (20 mg/kg) decreased CPP in male and female mice (n = 11-12/group) for a high (10 mg/kg) dose of cocaine (LMM-ANOVA: interaction Test:Virus: F_1,44 = 13.4504, p = 0.0006572, followed by Sidak’s post hoc tests).

(B) Experimental design for behavioral economics testing, using male rats (n = 6-8/group) treated systemically with HX531 (12 mg/kg).

(C) Dose-response curves in the threshold procedure showed decreased responding across doses of cocaine after HX531 treatment (LMM-ANOVA: main effect of Treatment: F_9,12 = 7.2432, p = 0.01962, followed by Sidak’s post hoc tests).

(D) Averaged demand curves showed decreased cocaine intake across cocaine prices (LMM-ANOVA: main effect of Treatment: F_9,12 = 5.4469, p = 0.0378, followed by Sidak’s post hoc tests).

(E) Representative example of task performance in the threshold procedure (from an HSV-GFP control), highlighting mathematical demand curve fitting and extraction of behavioral economics parameters.

(F) Consumption at low effort Q₀ (unpaired Welch’s t-test: t_11.218 = 1.1917, p = 0.258) was not affected by HX531 treatment.

(G) Consumption at maximum effort Q_max (unpaired Welch’s t-test: t_11.305 = 1.2226, p = 0.2463) was similarly not affected.

(H) Motivation metrics P_max (unpaired Welch’s t-test: t_7.953 = 2.8289, p = 0.0223) was decreased by HX531 treatment.

(I) Omax (unpaired Welch’s t-test: t_11.607 = 2.6369, p = 0.0222) was similarly decreased.

(J) Demand elasticity α was increased by HX531 treatment (unpaired Welch’s t-test: t_7.3526 = −3.0459, p = 0.01761).

Bar graphs and line graphs represent mean ± SEM.