Partial agonism at the α7 nicotinic acetylcholine receptor improves attention, impulsive action and vigilance in low attentive rats.
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 α7 nicotinic acetylcholine receptor (nAChR) induces attention deficits therefore selective agonism may improve attention, without the abuse liability associated with nicotine. The α7 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 0.3mg/kg encenicline, a reduction in impulsive action (probability of false alarms) and increase in vigilance following 1mg/kg at 0.75sSD. At 1mg/kg, HA animals had reduced selective attention at 0.75sSD and reduced vigilance at 0.75 and 1.25sSD. 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 α7 nAChR partial agonism may improve attention particularly in conditions with low attention.
Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Manchester M13 9PT, UK. Electronic address: andrew.hayward@manchester.ac.uk.
Andrew
A
Hayward
Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Manchester M13 9PT, UK.
Lisa
L
Adamson
Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Manchester M13 9PT, UK. Electronic address: joanna.neill@manchester.ac.uk.
Joanna C
JC
Neill
D000704:Analysis of Variance; D000818:Animals; D001288:Attention / Q000187:drug effects*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000235:genetics; D002755:Choice Behavior / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007175:Impulsive Behavior / Q000187:drug effects*; D008297:Male; D010775:Photic Stimulation; D011812:Quinuclidines / Q000627:therapeutic use*; D051381:Rats; D055647:Rats, Transgenic; D013830:Thiadiazoles / Q000627:therapeutic use*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists / Q000235:genetics / Q000378:metabolism
C000618299:ABT-126; D011812:Quinuclidines; D013830:Thiadiazoles; D064569:alpha7 Nicotinic Acetylcholine Receptor
5 choice-continuous performance task; 5C-CPT; Animal Model; Behavioural separation; Low attentive; α7 nAChR