Modeling ADHD: impulsivity, hyperlocomotion, and sensitivity to nicotine in the SHR strain of rat

ADHD is a childhood neurobehavioral disorder characterized by inordinate levels of hyperactivity, inattention and impulsivity. The inability to withhold a reinforced response, or response inhibition capacity (RIC), is one aspect of impulsivity associated with ADHD. The first goal of this dissertation was to evaluate the fixed minimum interval (FMI) schedule as a method for assessing RIC. Chapter 2 showed that latencies were substantially more sensitive than FMI-derived estimates of RIC to the effects of pre-feeding and changes in rate and magnitude of reinforcement. Chapter 3 examined the ability of the FMI to discriminate between spontaneously hypertensive rats (SHR), an animal model of ADHD, and Wistar Kyoto (WKY) controls. Results from Chapter 3 showed that RIC was not substantially different between SHR and WKY rats. However, latencies were significantly shorter for SHRs than for WKYs suggesting incentive motivation differed between strains. The second goal of this dissertation was to examine the sensitivity of the SHR to nicotine. ADHD is a risk factor for tobacco dependence. The goal of Chapters 4 and 5 was to determine whether the SHR provided a model of ADHD-related tobacco sensitivity. Chapter 4 examined nicotine's locomotor and rewarding effects in adolescent SHRs using the conditioned place preference (CPP) procedure. SHRs developed CPP to the highest nicotine dose tested and were sensitive to nicotine's locomotor-enhancing properties. WKY controls did not develop CPP to any nicotine dose tested and were not sensitive to nicotine's locomotor properties. However, it is likely that nicotine effects were obscured by a pseudo-conditioning to saline in WKYs. Chapter 5 demonstrated that SHRs were more active than WKYs in the open-field but not in the Rotorat apparatus. Results also showed that SHRs and WKYs were both sensitive to nicotine's locomotor sensitizing effects. However, WKYs were more sensitive than SHRs to nicotine's locomotor suppressing effects. Collectively, results from Chapters 4 and 5 show that SHRs are sensitive to the rewarding and locomotor-enhancing properties of nicotine. However, more research is necessary to confirm that SHRs are a suitable model for studying ADHD-related tobacco use.