Partial agonism at the alpha 7 nicotinic acetylcholine receptor improves attention, impulsive action and vigilance in low attentive rats

摘要

Inattention is a disabling symptom in conditions such as schizophrenia and attention deficit/hyperactivity disorder. Nicotine can improve attention and vigilance, but is unsuitable for clinical use due to abuse liability. Genetic knockout of the alpha 7 nicotinic acetylcholine receptor (nAChR) induces attention deficits therefore selective agonism may improve attention, without the abuse liability associated with nicotine. The alpha 7 nAChR partial agonist encenicline (formerly EVP-6124) enhances memory in rodents and humans. Here we investigate, for the first time, efficacy of encenicline to improve attention and vigilance in animals behaviourally grouped for low attentive traits in the 5 choice-continuous performance task (5C-CPT). Female Lister Hooded rats were trained to perform the 5C-CPT with a variable stimulus duration (SD). Animals were then grouped based on performance into upper and lower quartiles of d' (vigilance) and accuracy (selective attention), producing high attentive (HA) and low-attentive (LA) groups. LA animals showed an increase in selective attention and vigilance at 0.3 mg/kg encenicline, a reduction in impulsive action (probability of false alarms) and increase in vigilance following 1 mg/kg at 0.75 s SD. At 1 mg/kg, HA animals had reduced selective attention at 0.75 s SD and reduced vigilance at 0.75 and 1.25 s SD. Improvement of attention, vigilance and impulsive action in LA animals demonstrates that encenicline has pro attentive properties dependent on baseline levels of performance. Our work suggests that alpha 7 nAChR partial agonism may improve attention particularly in conditions with low attention. (C) 2017 Elsevier B.V. and ECNP. All rights reserved.