Fig. 4.

Isobolographic analysis of the effects of NAL and MTII administered in selected combinations. For this analysis, the ED₅₀ and 95% confidence levels (C.L.) for the effects of NAL (solid circle) and MTII (solid square) alone on binge-like ethanol drinking were plotted along the abscissa and ordinate, respectively. Then the ED₅₀ and 95% C.L. for drugs when tested in combination with the ED₂₀ or ED₃₀ of the other drug were plotted. The area between dashed lines that connect the 95% C.L. of the ED₅₀ for each drug alone represents the “area of additivity”, the area in which drug interactions were considered to be additive. The region to the left of the dashed line defines synergistic drug interactions. The data show that the low ED₂₀ dose of MTII (0.26 mg/kg) synergistically augmented the ability of NAL to blunt binge-like ethanol drinking, shifting the dose-response ED₅₀ value of NAL to the left beyond the area of additivity and into the region representing synergistic drug interactions. Neither the low ED₂₀ (0.82 mg/kg) nor high ED₃₀ (1.64 mg/kg) doses of NAL synergistically altered the ED₅₀ values for MTII-induced blunting of binge-like ethanol drinking, as the ED₅₀ for these drug dose combinations fell within the area of additivity.