Timing and delay discounting in attention-deficit/hyperactivity disorder: A translational approach.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that often presents with abnormal time perception and increased impulsive choice behavior. The spontaneously hypertensive rat (SHR) is the most widely used preclinical model of the ADHD-Combined and ADHD-Hyperactive/Impulsive subtypes of the disorder. However, when testing the spontaneously hypertensive rat from Charles River (SHR/NCrl) on timing and impulsive choice tasks, the appropriate control strain is not clear, and it is possible that one of the possible control strains, the Wistar Kyoto from Charles River (WKY/NCrl), is an appropriate model for ADHD-Predominately Inattentive. Our goals were to test the SHR/NCrl, WKY/NCrl, and Wistar (WI; the progenitor strain for the SHR/NCrl and WKY/NCrl) strains on time perception and impulsive choice tasks to assess the validity of SHR/NCrl and WKY/NCrl as models of ADHD, and the validity of the WI strain as a control. We also sought to assess impulsive choice behavior in humans diagnosed with the three subtypes of ADHD and compare them with our findings from the preclinical models. We found SHR/NCrl rats timed faster and were more impulsive than WKY/NCrl and WI rats, and human participants diagnosed with ADHD were more impulsive compared to controls, but there were no differences between the three ADHD subtypes.

Interventions aimed at changing impulsive choice in rats: Effects of immediate and relatively long delay to reward training.

A relatively strong preference for smaller-sooner rewards (SSR) over larger-later rewards (LLR) is associated with a host of maladaptive behavioral patterns. As such, the clinical implications for increasing preference for LLR are profound. There is a growing body of literature that suggests extended exposure to delayed reward may increase preference for LLR in rats. However, questions remain about the underlying mechanism driving this effect and the extent to which extended exposure to immediate rewards may decrease LLR choice. In Experiment 1, we tested effects of a differential-reinforcement-of-low-rates schedule (DRL) to increase LLR choice using a pretest/posttest design with Wistar rats as subjects. We compared this group to a group of rats exposed to a differential-reinforcement-of-high-rates schedule (DRH). The DRH intervention has never been employed in this research context, but explicitly programs an immediate response-reinforcement requirement. In Experiment 2, we tested effects of an intervention with a delay longer than those used in the delay discounting pretest and posttest. No previous research has tested effects of an intervention delay this long, relative to the delay discounting task. We compared this group to a group exposed to a delay that was part of the delay discounting pretest and posttest and to a group exposed to a traditional no-delay, fixed-ratio (FR) 2 control intervention. In both experiments, we found that exposure to delayed rewards in the intervention phase significantly increased LLR choice relative to pretest performance. These findings replicate and extend a growing body of literature showing that delay exposure increases preference for LLR. We also found significant decreases in LLR choice from pretest to posttest in the DRH and no-delay intervention groups in Experiments 1 and 2, respectively. This is the first report of such an effect and has implications for understanding and interpreting effects of delay exposure training in past and future research. Our results also suggested no relationship between improved temporal tracking of reward and increases in LLR choice as a result of delay exposure training.