Differential-reinforcement-of-low-rate (DRL) schedules have been used to evaluate the effects of a wide variety of drugs, including amphetamines, cannabanoids, and antidepressant medication. To earn a reinforcer, organisms operating under a DRL schedule are required to withhold a response for a predetermined amount of time before responding, and therefore this schedule maintains a low rate of responding and can be viewed as a response-inhibition task. In experiment 1, three different DRL schedules (4.5, 9.5, and 29.5 s) were used to evaluate systematically a range of nicotine doses (0.0, 0.1, 0.3, and 0.5 mg/kg). The dose–response effect of nicotine then was compared with the effects of increased reinforcer magnitude on responding. Both the administration of nicotine and increased reinforcer magnitude engendered less accurate DRL-schedule performance compared with baseline conditions, and the dose and magnitude-dependent shifts were most evident on the DRL 29.5-s schedule. Experiment 2 compared the differences between acute and chronic dosing regimens (0.3 mg/kg nicotine) on DRL 29.5-s schedule responding. After 20 consecutive sessions of nicotine dosing, accuracy deteriorated significantly, demonstrating that chronic nicotine dosing leads to a behavioral sensitization apparent on the DRL 29.5-s schedule. The results from both experiments suggest that responding on the DRL 29.5-s schedule is sensitive to both dose–response and regimen-dependent effects of nicotine.

A conjunctive variable-interval differential-reinforcement-of-low-rate (VI-DRL, n= 18) responding schedule and a stop-signal task (n= 18) were used to evaluate the disinhibiting effects of nicotine on response withholding in rats. Sucrose solution was used to reinforce responding, and after a stable baseline was achieved under saline-administration conditions, 0.3 mg/kg nicotine was delivered before each session. Experiment 1 showed that repeated, but not the initial, administration of nicotine decreased performance on both tasks, and the effect of sensitization followed a similar timeline; 10 consecutive doses resulted in poorer proportion-correct VI-DRL trials and percent correct stop trials than the initial dose of nicotine. Furthermore, sensitization to 0.3 mg/kg nicotine decreased performance regardless of whether a spaced or consecutive-dosing regimen was followed. Experiment 2 was designed to test whether mecamylamine hydrochloride (0.1–1.0 mg/kg) could attenuate the effects of repeated 0.3 mg/kg nicotine administration, and the degree to which mecamylamine attenuation of the effect of nicotine to produce impulsive action was relative to dose. Results from experiment 2 showed that response disinhibition, as evaluated using the VI-DRL and stop-signal tasks, is related in a systematic manner to nicotinic-acetylcholine receptor activation.