Response disinhibition evoked by the administration of nicotine and nicotine-associated contextual cues

Abstract

Nicotine causes dose-dependent alterations in accuracy on the differential-reinforcement of low-rate responding (DRL) 29.5-s schedule in rats. The current investigation evaluated whether nicotineassociated contextual cues can produce nicotine-like perturbations in DRL-schedule performance in the absence of nicotine. Nicotine and saline administrations occurred just prior to DRL 29.5-s schedule responding for sucrose solution, and two different experimental contexts (differentiated by visual, olfactory, and tactile cues) were utilized. All subjects (N = 16) experienced two consecutive daily sessions of DRL-schedule responding per day. The experimental group (n = 8) was exposed to saline immediately prior to the first session and 0.3mg/kg nicotine before the second session, and the context was changed between sessions. This sequence of saline and then nicotine administration, paired with two reliable contexts, persisted for 12 consecutive days and successive nicotine administrations corresponded with increasingly poorer performance on the DRL 29.5-s schedule. No nicotine was administered for days 13-20 during context testing, and the nicotine-associated context produced response disinhibition on the DRL schedule. Two control groups were included in the design; subjects in one control group (n = 4) received saline in each context to verify that the contexts themselves were not exerting control over operant responding. To assess how explicit and nonexplicit pairings of nicotine and contextual cues influenced DRL behavior, subjects in a second control group (n = 4) were given nicotine prior to the second session, but the contexts were not altered between sessions. The results from this experiment suggest that environmental stimuli associated with nicotine exposure can come to elicit nicotine-induced performance decrements on a DRL 29.5-s schedule.

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).…”

“…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).…”

Acute nicotine increases both impulsive choice and behavioural disinhibition in rats

“…Bizot 1998;Bizarro et al 2004;Blondel et al 2000;Hahn et al 2002;Kirshenbaum et al 2009;Mirza and Stolerman 1998;Popke et al 2000;Stolerman et al 2000;TsutsuiKimura et al 2010a, b). However, they are at variance with several other 5CSRTT studies that have failed to observe an increase in anticipatory responding (Day et al 2007;Hahn et al 2003;Mirza and Bright 2001).…”

“…Blondel et al 2000;Bizarro et al 2004;Day et al 2007;Harrison et al 1997;Mirza and Bright 2001;Mirza and Stolerman 1998;Stolerman et al 2000;Tsutsui-Kimura et al 2010a). An increase in inappropriate premature responding during a delayed reinforcement of low levels of responding (DRL) schedule of reinforcement has also been reported following acute nicotine administration (Bizot 1998;Popke et al 2000;Kirshenbaum et al 2009). However, this effect may be related to nicotine's known effects on time perception (e.g.…”

Chronic stress impairs prefrontal cortex-dependent response inhibition and spatial working memory.

“…Response inhibition capacity, or the ability to withhold a reinforced response, is a type of impulse control of particular interest because of its relation to attention deficit hyperactivity disorder (Barkley, 1997), cognitive aging (Braver & Barch, 2002), and drug addiction (Li & Sinha, 2008). Among the current methods used to investigate response inhibition are response-withholding paradigms, such as the differential reinforcement of low rates schedule (DRL) and the lever holding task (Ferguson et al, 2007; Kirshenbaum, Johnson, Schwarz, & Jackson, 2009; Sanabria & Killeen, 2008). In these paradigms, rats are required to make an initial response and then withhold a terminal response for a designated amount of time before receiving a reward; premature terminal responses restart the schedule without yielding a reward.…”