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.

Stimulus control in two rodent models of attention-deficit/hyperactivity disorder.

The spontaneously hypertensive (SHR/NCrl) rat from Charles River is one of the most widely used models of the combined subtype of Attention-Deficit/Hyperactivity Disorder (ADHD-C). Although often used as its control strain, the Wistar Kyoto (WKY/NCrl) from Charles River has been proposed as a model of the predominately inattentive subtype of ADHD (ADHD-PI). In Experiment 1 SHR/NCrl, WKY/NCrl, and Wistar (WI; the progenitor strain for the two models) rats were trained on a left→right lever-press sequence in the presence of light discriminative stimuli that signaled the active lever in the sequence. In subsequent conditions the discriminative light cues were removed or reversed. WKY/NCrl accuracy remained relatively stable across cue light transitions. SHR/NCrl and WI accuracy was more disrupted when light cues were removed or reversed-an indication that behavior of the WKY/NCrl rats may not have come under control of the discriminative light cues as it did for the other strains, but relied more on past behavior and spatial cues. In Experiment 2, all three strains were exposed to a response-initiated fixed-interval (RIFI) 8-s schedule of reinforcement. In RIFI schedules behavior must be timed from a past instance of the target response. Replicating previous work, timing during the FI was roughly equivalent across the three strains; however, latencies to initiate the FI were significantly longer for SHR/NCrl than WKY/NCrl and WI rats, suggesting SHR/NCrl behavior was less sensitive to the first-response:food contingency in the RIFI schedule. These findings identify differences in stimulus control between the three strains and may help determine the efficacy of SHR/NCrl and WKY/NCrl as models of ADHD subtypes in humans.