Nicotine-induced behavioral sensitization in an adult rat model of attention deficit/hyperactivity disorder (ADHD)

Abstract

Attention deficit hyperactivity disorder (ADHD) is associated with increased risk of tobacco dependence. Nicotine, the main psychoactive component of tobacco, appears to be implicated in ADHD-related tobacco dependence. However, the behavioral responsiveness to nicotine of the prevalent animal model of ADHD, the spontaneously hypertensive rat (SHR), is currently underinvestigated. The present study examined the activational effects of acute and chronic nicotine on the behavior of adult male SHRs, relative to Wistar Kyoto (WKY) controls. Experiment 1 verified baseline strain differences in open-field locomotor activity. Experiment 2 tested for baseline strain differences in rotational behavior using a Rotorat apparatus. Adult SHR and WKY rats were then exposed to a 7-day regimen of 0.6 mg/kg/d s.c. nicotine, or saline, prior to each assessment. A separate group of SHRs underwent similar training, but was pre-treated with mecamylamine, a cholinergic antagonist. Nicotine sensitization, context conditioning, and mecamylamine effects were then tested. Baseline strain differences were observed in open-field performance and in the number of full rotations in the Rotorat apparatus, but not in the number of 90° rotations or direction changes. In these latter measures, SHRs displayed weaker nicotine-induced rotational suppression than WKYs. Both strains expressed nicotine-induced sensitization of rotational activity, but evidence for strain differences in sensitization was ambiguous; context conditioning was not observed. Mecamylamine reversed the effects of nicotine on SHR performance. These findings are consistent with the hypothesis that a reduced aversion to nicotine (expressed in rats as robust locomotion) may facilitate smoking among adults with ADHD.

Evidence of Altered Brain Responses to Nicotine in an Animal Model of Attention Deficit/Hyperactivity Disorder

“…Selective strain differences in the impact of nicotine (pre-vs. postadministration) included an increase in rsFC in the RSP-VTA circuit in the ADHD model, the SHR, while having the opposite effect in the control strains. It is tempting to speculate that this enhancement of VTA functional connectivity may underlie enhanced rewarding properties of nicotine, 53,54 or even the dampened aversive properties, 55 even though we did not observe rsFC changes in the VTA-NAcc circuit (Table 1).…”

Neuroinflammation and insulin resistance underly cognitive impairment. Sex differences and potential treatments

“…One of the main and characteristic symptoms in ADHD is the spontaneous locomotor hyperactivity and it has been shown in mice [388] , rats [411] and humans [412] . We used the open filed paradigm to evaluate spontaneous locomotor hyperactivity in our model.…”