Differential-reinforcement-of-low-rate-schedule performance and nicotine administration: a systematic investigation of dose, dose-regimen, and schedule requirement

Abstract

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.

Detrimental effects of acute nicotine on the response-withholding performance of spontaneously hypertensive and Wistar Kyoto rats

“…This result suggests that acute nicotine reduces response inhibition capacity in both strains. Although this finding is inconsistent with our expectations, it is consistent with nicotine-induced reductions in IRTs observed in DRL studies using Sprague Dawley rats (Kirshenbaum et al 2008, 2009, 2011). Performance in DRL schedules cannot be readily interpreted in terms of response inhibition capacity, because it is also sensitive to reinforcer-efficacy manipulations (e.g., reinforcer magnitude; Doughty and Richards 2002).…”

“…Treatment was implemented twice per week, with at least 2 rest days between treatments. This drug regimen was chosen because neither tolerance nor sensitization effects were evidenced in a similar regimen implemented by Kirshenbaum et al (2008) using DRL 4.5-s and Sprague Dawley rats. Within this range of doses, acute s.c. nicotine disrupts DRL performance (Kirshenbaum et al, 2008), timing (Hinton and Meck, 1996), improves performance in 5-CSRTT (Bizarro and Stolerman 2003; Hahn et al 2003), induces place preference, and enhances social rewards (Thiel et al 2009).…”

“…Unlike humans, acute nicotine administration in rodents consistently decreases response inhibition capacity in a wide range of tasks, including the 5-CSRTT (Bizarro et al 2004; Blondel et al 2000; Hahn et al 2002; Semenova et al 2007), the differential reinforcement of low rates (DRL) schedule of reinforcement (Kirshenbaum et al 2011; Kirshenbaum et al 2009; Kirshenbaum et al 2008; Popke et al 2000a; Popke et al 2000b), the stop-signal task (Kirshenbaum et al 2011), and the go/no-go discrimination (Kolokotroni et al 2011). Only the temporal response differentiation task, which involves holding down a lever for a target interval, appears to be insensitive to nicotine-induced premature responding (Popke et al 2000b).…”

Validation of a method to assess ADHD-related impulsivity in animal models

“…Moreover, changes in motivation appear to influence RIC indices in 5-CSRTT (Bizarro & Stolerman, 2003) and in DRL (Conrad, Sidman & Herrnstein, 1958; Holz & Azrin, 1963; Tanno, Kurashima & Watanabe, 2011; Beer & Trumble, 1965; Doughty & Richards, 2002; Kirshenbaum, Brown, Hughes, & Doughty, 2008). These findings suggest a reduced specificity of the 5-CSRTT and the DRL tasks to changes in RIC.…”

Prenatal exposure to vapors of gasoline–ethanol blends causes few cognitive deficits in adult rats

“…DRL schedules require animals to withhold pressing a lever for a predetermined amount of time before a lever-press produces food. This schedule thereby maintains a low rate of responding and has been used extensively as a test of response inhibition (Popke et al, 2000;Kirshenbaum et al, 2008;Sanabria and Killeen, 2008). A lack of response inhibition on Fig.…”