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Rats given continuous access to etonitazene hydrochloride in their drinking water (5 micrograms per milliliter) more than doubled their drug intake while deprived of food. Another group of rats with implanted jugular catheters self-administered etonitazene (10 micrograms per kilogram) intravenously on a continuous reinforcement schedule, and the number of infusions increased significantly on days when they were deprived of food. These results suggest that feeding condition may be a powerful determinant of drug-reinforced behavior.

Relative persistence of behavior is measured in terms of rates of behavior at a higher schedule value divided by rates of behavior at a lower schedule value and then multiplied by 100 to express the result as a percentage. Relative persistence of behavior is a direct function of reinforcer size over a broad range of values. In 1 study, food was the reinforcer; however, in most studies of persistence, drug reinforcers were used, and the drugs were taken orally or intravenously. A variety of reinforcing drugs were studied: barbiturates, opioids, psychomotor stimulants, a dissociative anesthetic, and alcohol. Both ratio and interval schedules were used to study relative persistence of behavior in human participants, male and female rhesus monkeys (Macaca mulatta), and rats. Thus, studies of persistence are based on results of an extensive set of conditions. The results support the proposition that relative persistence of behavior is a fundamental measure of relative reinforcing effects.

Performances of three rhesus monkeys were reinforced by the oral delivery of pentobarbital and studied as functions of fixed-ratio size and drug concentration. Pentobarbital solutions and water were concurrently available on identical reinforcement schedules from separate liquid-delivery systems during 3-hour sessions. Under a fixed-ratio 16 schedule of drug availability, a descending series of drug concentrations was tested (4, 2, 1, 0.5, 0.25, 0.125, and 0.0625 mg/ml, followed by a retest at 4 mg/ml). Partial concentration series beginning with the highest concentration were repeated with fixed-ratios of 32 and 64, with a fixed-ratio 128 for two monkeys, and with fixed-ratio 256 for one. At each fixed-ratio value, response rate and number of drug deliveries were inverted U-shaped functions of pentobarbital concentration. Drug intake (mg/kg/session) increased directly with drug concentration. As the fixed-ratio size was increased, the number of liquid deliveries decreased. For each drug concentration, when the numbers of drug deliveries at fixed-ratios of 32, 64, and 128 responses were plotted as percentages of those obtained at fixed-ratio 16, the following orderly relationship emerged: the higher the drug concentration, the less that drug deliveries were decreased by increases in fixed-ratio size. This relationship indicates an increase in reinforcing efficacy with increases in pentobarbital concentration.

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Methadone and cigarette puffs appear to be asymmetric economic complements.

Response-contingent deliveries of oral pentobarbital maintained responding of 3 rhesus monkeys during daily 3-hr sessions. Deliveries of pentobarbital were arranged under nonindependent concurrent variable-ratio variable-ratio schedules. Responses to either schedule counted toward completion of both variable-ratio schedule requirements. This schedule is similar in some respects to conventional concurrent variable-interval variable-interval schedules, in which passage of time counts toward completion of the interval value on both schedules. Restricted nonindependent concurrent variable-ratio variable-ratio schedules were also studied. On that schedule, when a drug delivery was assigned to one spout, it had to be collected before responses on the opposite spout again counted toward completion of the schedule requirements. Relative reinforcer magnitude was varied by changing the drug concentration on one schedule while keeping the drug concentration constant on the other variable-ratio schedule. Under both types of concurrent variable-ratio variable-ratio schedules, the relative rate of responding corresponded to the relative drug intake. Unlike earlier studies of concurrent variable-interval variable-interval intravenous cocaine reinforcement, preference was proportionate to concentration, and exclusive preferences did not develop. The relationship between relative rate of responding and relative drug intake was well described by the generalized matching law.