Reinforcing effects of contingently administered subcutaneous injections of etonitazene in rats

Rationale: Response-contingent injections of opioids have been shown to con trol behavior in various species. Objective: To determine whether s.c. inje ctions of etonitazene (ETZ) could maintain behavior in rats when administer ed under a single fixed-interval schedule. Methods: Rats were trained to le ver press for eight 45-mg food pellets under a single fixed-interval (FI) 1 0-min schedule of reinforcement: following passage of the 10-min interval, each lever press resulted in a pellet delivery until eight pellets were obt ained. Delivery of the reinforcer was signaled by a change in visual stimul us conditions. Once stable responding for the food pellets under the FI 10- min schedule was established, a s.c. injection of 3.2 mug/kg ETZ was admini stered to the rat by the investigator following schedule completion and del ivery of the food pellets. After receiving the drug injection, rats were re turned to the experimental chamber for 30 min and exposed to the same stimu lus conditions that accompanied food reinforcement. Across sessions, the nu mber of food pellets was decreased until rats were responding solely for th e drug. Results: Responding for the s.c. administered drug stabilized and p ersisted across sessions. When saline vehicle injections were substituted f or the drug injections, responses diminished across sessions to levels belo w that of the drug baseline. Subsequent alternating blocks of ETZ and vehic le injections produced respective increases and decreases in responding. Co nclusion: This study demonstrates that response-contingent s.c. injections of a drug can control behavior in rats, systematically replicating a previo us experiment that used the i.p. route. Since all pertinent operant behavio r is emitted prior to the administration of drug, this procedure can be use d for testing the reinforcing effects of a drug without interference from a ny direct (rate-altering) drug effects. The present findings also extend th e conditions under which drugs of abuse may reinforce behavior.