Relationship between response rates and measures of reinforcing strength using a choice procedure in monkeys

Abstract

Concurrent schedules of reinforcement are increasingly being used to investigate the reinforcing strength of abused drugs. A purported advantage of concurrent schedules is that the primary dependent measure, percentage of responses emitted on the drug-associated manipulandum, is independent of the rate-altering effects of drugs. Data supporting this hypothesis are, however, rarely presented, which was one goal of this study. In addition, we tested the hypothesis that drug-induced decreases in response rates provides an additional index to characterize abuse liability of drugs. This study examined the relationship between response rate and response allocation (i.e. drug choice) when 3,4-methylenedioxymethamphetamine (MDMA, 0.03-0.3 mg/kg/inj) or cocaine (0.003-0.1 mg/kg/inj) was the alternative to food under concurrent fixed-ratio reinforcement schedules in rhesus (n=4) and cynomolgus (n=16) monkeys, respectively. Increasing doses of MDMA or cocaine resulted in increased drug choice and dose-dependent decreases in overall response rates. For both drugs, response rates on the drug-associated lever were not affected by dose and were not different from saline. Furthermore, at most doses, rates of responding on the food-associated lever were significantly higher than response rates on the drug-associated lever. Finally, MDMA but not cocaine decreased food-reinforced responding, providing evidence for potential differences between the drugs. These results demonstrate that under concurrent food-drug reinforcement schedules, response rates on the drug-associated lever are independent of measures of reinforcement, whereas disruptions in food-maintained responding may be inversely related to abuse liability.

Figure 1

Food- and drug-maintained and overall response rates during availability of (A) food and cocaine or (B) food and MDMA under concurrent FR schedules of reinforcement. Data points represent mean ± SEM (n=16 for cocaine; n=4 for MDMA). Vertical axis: response rates on the drug- (filled squares) and food-associated (filled circles) levers and overall (open triangles) response rates. Horizontal axis: drug dose (mg/kg/inj). ^* significantly different from the lowest available drug dose (0.003 mg/kg/inj for cocaine; 0.03 mg/kg/inj for MDMA; p < 0.05).