Δ9-Tetrahydrocannabinol interactions with phencyclidine and ethanol: Effects on accuracy and rate of responding

Abstract

The effects of Δ 9-tetrahydrocannabinol ( Δ 9-THC) in combination with phencyclidine (PCP) or ethanol were examined in rats responding under a fixed-consecutive-number schedule of food presentation. Under this schedule, a minimum of 13 consecutive responses on one lever followed by one response on another lever produced food. When administered alone, PCP (0.1–10.0 mg/kg) and Δ 9-THC (0.1–5.6 mg/kg), but not ethanol (0.3–1.7 g/kg), decreased accuracy. PCP, Δ 9-THC, and ethanol alone all produced dose-dependent decreases in rate of responding. A dose-effect curve for PCP or ethanol was then redetermined in combination with selected doses of Δ 9-THC (0.125–1.75 mg/kg) and the data were analyzed according to the effect-addition and dose-addition models of additivity. When administered in combination, Δ 9-THC produced dose-dependent leftward shifts in the PCP dose-effect curves for both accuracy and rate of responding. The interactions for PCP + Δ 9-THC combinations were effect-additive for accuracy. In contrast, the type of interaction obtained for PCP + Δ 9-THC combinations on rate of responding depended upon the particular doses combined, as well as on the model used to analyze the interactions. According to the effect-addition model, these interactions were additive at low doses of Δ 9-THC and supraadditive at the highest dose. However, according to the dose-addition model the interactions at the higher doses of Δ 9-THC were infraadditive. Δ 9-THC also shifted the ethanol dose-effect curve for rate of responding to the left but did not alter the ethanol dose-effect curve for accuracy. The interactions for ethanol + Δ 9-THC combinations were effect-additive for accuracy and both effect- and dose-additive for rate of responding. The present investigation clearly illustrates the importance of examining an extensive range of dose combinations on different behavioral measures, as well as the use of appropriate analyses in studies designed to evaluate the interactions between drugs.