Timing and space usage are disrupted by amphetamine in rats maintained on DRL 24-s and DRL 72-s schedules of reinforcement

Abstract

Rationale A differential-reinforcement-of-low-rate schedule (DRL) delivers reinforcement only when the interresponse time (IRT) exceeds a fixed time interval, thereby shaping rats to discriminate the timing of their responses. However, little is known about the motor behavior and location of the rats in the chamber during the IRTs that lead to reinforcement. Although amphetamine is known to disrupt DRL timing behavior, the effects of this drug on non-operant motor behavior during DRL performance has not yet been quantified. Objective The purpose of this research was to measure the motor behavior (movement trajectories in the horizontal plane and spatial location in the plane) during longer IRT’s after either vehicle or amphetamine treatment. Method Experimental chambers were constructed with a force-plate actometer as the floor, and while performing the operant task, the rats’ motor behaviors were measured continuously with high temporal and spatial resolution. Separate groups of 8 male Sprague Dawley rats were maintained on either DRL 24-s or DRL 72-s schedules of water reinforcement in 4-hr recording sessions. Results Analyses of IRT distributions showed that the rats’ timing behavior conformed to their respective DRL requirements. In the absence of drug, analysis of motor behavior in pre-reinforcement intervals showed that rats located themselves away from the operandum, and exhibited very low levels of movement. Rats exhibited a significant temporal diminution of horizontal movement that reached a minimum 4–8 s before the rats moved to the operandum to execute operant responses. Amphetamine treatment increased locomotion, abolished the temporal movement gradient, and brought the rats closer to the operandum compared to vehicle treatment. Movement changes induced by amphetamine were accompanied by degraded timing behavior. Conclusions Taken together, the data show that DRL training induced rats to locate themselves away from the operandum and to remain nearly motionless during longer IRTs, and that amphetamine treatment interfered with this complex of behavioral features

Opposite Effects of Amphetamine on Impulsive Action with Fixed and Variable Delays to Respond

“…If this were true, increased premature responding could simply be an exacerbation of the normal, anticipatory responses we observed in the Fixed 4-s condition. In agreement with this idea, amphetamine increases premature responses in other tasks with consistent delays, such as the 5-CSRTT (Cole and Robbins, 1987;Harrison et al, 1997;van Gaalen et al, 2006) and DRL tasks (Seiden et al, 1979;Lobarinas and Falk, 1999;Bizot 1998;Fowler et al, 2009), but not in the stop task which uses a variable delay to the signal for RI (Feola et al, 2000;Eagle and Robbins, 2003). Disruptions in timing abilities would not affect performance in the Variable condition, so it is not surprising that we failed to observe an amphetamine-induced increase in impulsive action in this version of the task.…”

“…That is, even though the length of the delay interval was predictable, subjects did not exhibit anticipatory responding toward the end of the interval. It is unlikely that the difference in these two patterns reflects an ability to time short (4 s) but not long (60 s) intervals as rats responding under DRL schedules can accurately assess delays of the longer duration (Seiden et al, 1979;Lobarinas and Falk, 1999;Bizot 1998;Fowler et al, 2009). The DRL task differs from the fixed delay version of the RI task in that the delay period in the latter is signaled.…”

“…Animal models of impulsivity (Dalley et al, 2011) support a central role for these neurotransmitters (Pattij and Vanderschuren, 2008), although the effect of amphetamine on impulsive actions in rats remains inconclusive. Specifically, amphetamine increases premature responding in the five-choice serial reaction time task (5-CSRTT; Cole and Robbins, 1987;Harrison et al, 1997;van Gaalen et al, 2006) and produces a leftward shift of inter-response times (IRTs) using differential reinforcement of low rate (DRL) schedules (Seiden et al, 1979;Lobarinas and Falk, 1999;Bizot 1998;Fowler et al, 2009), both indicative of increased impulsivity. In contrast, amphetamine improves performance (ie, decreases impulsive action) in the stop task (Feola et al, 2000;Eagle and Robbins, 2003), but only in subjects with high baseline (ie, slow) stop-signal reaction times.…”

The Utility of Impulsive Bias and Altered Decision Making as Predictors of Drug Efficacy and Target Selection: Rethinking Behavioral Screening for Antidepressant Drugs

“…Independent laboratories have replicated amphetamineinduced impulsivity for the 5-CSRTT (Pattij et al, 2007;Paterson et al, 2011b;Baarendse and Vanderschuren, 2012). For DRL 72-second behavior, amphetamine-induced increases in impulsivity have been suggested by increased response rates and cohesive leftward shift in the IRT distribution, including decreased peak latency (Balcells-Olivero et al, 1998;Fowler et al, 2009;Paterson et al, 2011a).…”

“…The shape of the IRT distribution means that usually less than 15% of total lever presses are followed by availability of a water (or food) reinforcer. Under control conditions, Fowler et al (2009) have suggested that rats responding on a DRL 72-second schedule locate themselves away from the operant lever and tend to exhibit very little movement. Only in the approximately last 8 seconds prior to a reinforced or unreinforced response did the rats exhibit an increased amount of horizontal locomotion.…”