title: ABT-594 improves performance in the 5-choice serial reaction time task under conditions of increased difficulty, sub-chronic dosing, and in poorly-performing subjects.
abstract: Several studies have tested nicotinic receptor ligands in the 5-Choice Serial Reaction Time Task (5-CSRTT) with varying results. Some investigators have increased attentional demands by modifying task parameters or using aged or poor performing rats to observe treatment effects. This study examined the alpha4beta2 nicotinic agonist ABT-594 in the 5-CSRTT using a variety of manipulations to determine optimal conditions for observing enhancement. ABT-594 had no effect in drug-naïve adult rats that self-initiated trials. Constant trial presentation decreased accuracy and omissions, with the latter significantly attenuated by acute administration of ABT-594 (0.019-0.062 micromol/kg). Sub-chronic treatment (0.019 micromol/kg) initially impaired drug-naïve subjects, but significant improvements in accuracy and decreased omissions were observed after 5 days of dosing. In 18-22 month-old rats, attentional demands were altered by interspersing blocks of trials with different stimulus durations. Acute ABT-594 (0.062 micromol/kg) enhanced accuracy performance in poor performing rats (<70% accuracy) but not in those that performed well (>80% accuracy), while omissions were decreased in both groups. Sub-chronic treatment with (0.019 micromol/kg) decreased omissions in all rats, but enhanced accuracy primarily in poor performing rats. These experiments demonstrate that an alpha4beta2 nicotinic agonist can enhance attention, but accuracy effects may only be observed under specific conditions. Moreover, a reduction in omissions was more reliably observed than improvements in accuracy, resulting in a net increase in signals successfully detected.
authors.affiliation: Neuroscience Research, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6115, USA. Eric.Mohler@abbott.com
authors.forename: Eric G
authors.initials: EG
authors.lastname: Mohler
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Franklin
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Rueter
authors.forename: Gerard B
authors.initials: GB
authors.lastname: Fox
authors.forename: Michael W
authors.initials: MW
authors.lastname: Decker
authors.forename: Kaitlin E
authors.initials: KE
authors.lastname: Browman
mesh_terms: D000818:Animals; D001384:Azetidines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011930:Reaction Time; D011978:Receptors, Nicotinic / Q000187:drug effects*
chemical_list: C109763:5-(2-azetidinylmethoxy)-2-chloropyridine; D001384:Azetidines; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2