Detrimental effects of acute nicotine on the response-withholding performance of spontaneously hypertensive and Wistar Kyoto rats

Rationale: Attention-deficit hyperactivity disorder (ADHD) is associated with a higher prevalence of smoking, which may be related to potential therapeutic effects of nicotine on ADHD symptoms. Whereas nicotine offers robust improvements in sustained attention, the effects of nicotine on impulsivity are unclear. Objectives: The present study examined the effects of nicotine on the response inhibition capacity of spontaneously hypertensive rats (SHR), an animal model of ADHD, compared to that of a normotensive control Wistar Kyoto (WKY), using the fixed minimum interval (FMI) schedule of reinforcement. Methods: Tests were conducted following acute injections of subcutaneous nicotine (0.1-0.6 mg/kg). On each FMI trial, the first lever press initiated an inter-response time (IRT); a head entry into a food receptacle terminated the IRT. IRTs longer than 6 s were intermittently reinforced with sucrose. Results: A model that assumes that only a proportion of IRTs are sensitive to the timing contingencies of the FMI provided a close fit to the data, regardless of strain or treatment. No baseline difference in FMI performance was observed between SHR and WKY. Nicotine reduced the duration of timed IRTs and the duration of latencies to the IRT-initiating lever press similarly for both strains. Nicotine dose-dependently increased the proportion of timed IRTs; the dose-response curve was shifted leftwards in SHR relative to WKY. Conclusions: These results suggest that nicotine (a) reduces response-inhibition capacity, (b) enhances the reinforcing efficacy of sucrose, and (c) dose-dependently enhances attention-like sensitivity to contingencies of reinforcement, through mechanisms that are yet unknown.