Figure 1. Tolerance to WIN55,212-2 (WIN)-mediated inhibition of glutamate and GABA release in the NAc. A1, The N2 component (small arrow) of the extracellular response is reversibly eliminated by DNQX (10 μm) and is concentration-dependently reduced by WIN55,212-2 in control (Con) slices. Note that neither compound altered the nonsynaptic N1 component (large arrow). Dashed horizontal lines in A define the baseline response. A2, Concentration-response curve for PS inhibition in slices from rats after chronic vehicle (•;EC50 = 143 nm), WIN55,212-2 (□;EC50 = 1.18 μm), or Δ9-THC (○;EC50 = 1.22 μm). Each point represents the mean ± SEM of three to nine slices. B1, Traces of eIPSCs and inhibition by 500 nm WIN55,212-2 in slices from a vehicle (Veh)-treated, WIN55,212-2-treated, and Δ9-THC-treated animals. B2, Summary of the inhibition of eIPSCs by WIN55,212-2 in slices from animals treated with vehicle (500 nm, n = 4; 1 μm, n = 3), WIN55,212-2 (500 nm, n = 5; 1 μm, n = 3), and Δ9-THC (500 nm, n = 5) (***p < 0.001 versus control; one-way ANOVA and post hoc comparison). C, Stimulus intensity versus PS amplitude relationship in slices from vehicle-treated (control), WIN55,212-2-treated, and Δ9-THC-treated rats. No differences among the groups were observed.