Measurement of the lowest dosage of phenobarbital that can produce drug discrimination in rats

Abstract

Accurate measurement of the threshold dosage of phenobarbital that can produce drug discrimination (DD) may improve our understanding of the mechanisms and properties of such discrimination. This study aimed to compare three methods for determining the threshold dosage for phenobarbital (D) versus no-drug (N) DD. Rats learned a D versus N DD in two-lever operant training chambers. A titration scheme was employed to increase or decrease dosage at the end of each 18-day block of sessions depending on whether the rat had achieved criterion accuracy during the sessions just completed. Three criterion rules were employed, all based on average percent drug lever responses during initial links of the last six D and six N sessions of a block. The criteria were: D% > 66 and N% < 33; D% > 50, and N% < 50; (D% - N%) > 33. Two squads of rats were trained, one immediately after the other. All rats discriminated drug versus no drug. In most rats, dosage decreased to low levels and then oscillated near the minimum level required to maintain criterion performance. The lowest discriminated dosage significantly differed under the three criterion rules. The squad that was trained second may have benefited by partially duplicating the lever choices of the previous squad. The lowest discriminated dosage is influenced by the criterion of discriminative control that is employed and is higher than the absolute threshold at which discrimination entirely disappears. Threshold estimations closer to absolute threshold can be obtained when criteria are employed that are more permissive of errors and that allow rats to maintain lever preferences.