Behavioral economic analysis of the effects of AHN 1‐055 and JHW 007, atypical dopamine uptake inhibitors, on cocaine self administration

Abstract

Benztropine analogs and other atypical dopamine uptake inhibitors selectively decrease cocaine self‐administration in rats at doses that do not affect responding maintained by other reinforcers. In the current study a behavioral economic approach was employed to further characterize the behavioral mechanisms of effects of benztropine analogs (AHN 1‐055, JHW 007) on responding maintained by cocaine injection in rats. Behavioral economic analyses represent a translational approach that take into account the price of the reinforcer as an important determinant of consumption. Two groups of rats were trained to respond for food (45 mg pellet) or cocaine (0.32 mg/kg/inj) under a fixed‐ratio (FR) 5 schedule in experimental sessions comprising five 20‐min components. In selected sessions the FR value was increased (5, 10, 20, 40, 80) during successive components to determine demand curves, which plot consumption (reinforcers obtained) against price (FR value). An exponential function was fitted to the data to derive the consumption at zero price (Q0) and the rate of decrease in consumption (essential value). AHN 1‐055 (1.78–10 mg/kg, IP), JHW 007 (3.2–10 mg/kg, IP) or vehicle was administered immediately before each demand curve determination. Consumption of cocaine or food decreased as the price (FR requirement) increased. At low doses AHN 1‐055 shifted downward and to the right the cocaine and the food demand curves. A larger dose shifted the curves leftward and downward. Analysis of the demand curve parameters indicated that AHN 1‐055 had equivalent effects on the essential value of cocaine or food but was more effective in decreasing Q0 for cocaine (%Δ= −83%) compared to food (%Δ=−27%). The effects of JHW 007 were less than those of AHN 1‐055, with only trends for decreases in Q0 for cocaine, and no significant difference in essential value for cocaine or food. Therefore, AHN 1‐055, but not JHW 007, selectively decreased consumption at zero price. The current findings obtained using an approach that takes in account the price of the reinforcer, indicate that AHN 1‐055 might be more effective than JHW 007 in reducing selectively consumption of cocaine.Support or Funding InformationThis work was supported by NIDA Intramural Research Program