Factors regulating drug cue sensitivity: the effects of dose ratio and absolute dose level in the case of fentanyl dose-dose discrimination.

This study presents a parametric analysis of the difference case in drug discrimination; rats were trained to discriminate a higher training dose of fentanyl, a narcotic analgesic, from a lower dose. Two parameters of dose-dose discrimination were investigated. First, dose ratio indicates the magnitude of the difference, expressed as a ratio, between the higher and the lower of the two training doses; dose ratios were 2, 4, 8, and 16 in four groups of animals. The second parameter is the absolute level of fentanyl dose at which any given ratio can be discriminated; in all four groups, the higher of the two training doses was progressively lowered from 0.04 to 0.00125 mg/kg. It was found that dose-dose discriminability of fentanyl was proportional to dose ratio in the entire 2 to 16 range of dose ratio, and that discriminability decreased monotonically as the absolute dose level was lower. Bias in discriminative responding was determined by absolute dose level only; dose ratio exerted no effect. The slope of the fentanyl generalization gradient increased as the dose ratio was smaller, and decreased as the absolute dose level was lower. Both dose ratio and absolute dose level also exerted effects on the ED50-value, but the effects of dose ratio were apparent only at higher training doses of 0.04 to 0.01 mg/kg. The data are consistent with the suggestion that fentanyl-saline discrimination is a special case of dose-dose discrimination; it is similar to the case where the higher of two training doses differs about 16-fold from the lower one. At this point, the lower training dose produces only liminal effects.