A novel nine-choice serial reaction time paradigm in rats: effects of nicotine on titrated performance

W.H.I.M. Drinkenburg¹, R. Roobol², A.B. Keith³, A. Sahgal³ and J.S. Andrews¹

¹ Organon Laboratories Ltd., Newhouse, Lanarkshire, United Kingdom
² NICI, University of Nijmegen, Nijmegen, The Netherlands
³ MRC Neurochemical Pathology Unit, Newcastle-upon-Tyne, United Kingdom

Serial reaction time tasks are valuable paradigms for studying attentional processes and deficits. In contrast to the five-choice serial reaction time paradigm, to our knowledge no study has been published wherein attentional performance of rats was challenged by presenting nine choices. Our study investigated in rats whether a nine choice paradigm can yield consistent performance and is sensitive to pharmacological manipulation by nicotine.

Male random bred rats (Charles River, UK) were maintained at 85% of their free-feeding weights (425-590g). Training and testing was done in chambers (25x25cm) each with one concave wall with 9 apertures, each 2.5cm square, 4cm deep and set 2cm above floor level. Holes were equipped with photocell beams monitoring nose entrance and could be occluded by a metal cap. Precision food pellets were delivered at the opposite side of the box into a photocell-monitored foodtray. The holes and the magazine could be illuminated (green multifocal LED, RS) and each box had a roof-mounted house-light. Boxes were separately housed in a dark, soundproof compartment, ventilated by low-noise fans. Procedure and data collection were controlled by in-house-developed software (Arachnid; Paul Fray).

The behavioral procedure consisted of five phases:

• Magazine training: With occluded apertures, food pellets were placed in the illuminated magazine.
• Nose-poke training: In each of five sessions of 20 trials just one hole (1, 3, 5, 7 or 9) was exposed and illuminated in a pseudo-random order. A nose-poke was rewarded with a pellet.
• Nose-poke training with light-tracking: As before, but reinforcement was conditional upon the cue-light in the aperture. After collection of the pellet a 4-8s intertrial interval (ITI) started. Responses in the aperture during the ITI were recorded as anticipatory responses and resulted in 10s time-out.
• Five-choice-serial-reaction-time-task: Five holes (1, 3, 5, 7, and 9) were exposed in each trial and after an ITI only one hole was illuminated pseudo-randomly to ensure 20 illuminations in each aperture over 100 trials. A response within five seconds in the (correct) illuminated aperture was rewarded; an incorrect or a preservative response resulted in a time-out period. A tray-visit initiated the next trial.
• Nine-choice-serial-reaction-time-task with titration: Nine holes were exposed and stimulus duration was eight seconds. Once performance was stable (three sessions in a row <25% omissions; >80% accuracy; >50 trials) stimulus duration became four seconds and titration started. A titration session consisted of six 18 trials blocks, each with two pseudo-random illuminations in each hole. After each block, stimulus duration was multiplied by 0.9 if accuracy was over 80% and number of omissions under 25%, else stimulus duration was multiplied by 1.1.

Variables analyzed included accuracy, latency-to-response, latency-to-magazine-visit, anticipatory responses; preservative responses; errors-of-omission. Drug administration: Nicotine (0.0; 0.05; 0.2; 0.8 mg/kg; n=6) was administered intraperitoneally 30 minutes prior to behavioral testing.

The acquisition curve of this task is shown in fig. 1: after three weeks of training in phase 5, animals obtained a mean stimulus duration of 0.544s (sem 0.0478s; range 0.30s-0.75s). None of the doses of nicotine had effect on performance, which suggests that animal’s performance was both stable and optimal.

The nine-choice-serial-reaction-time task is a well-controlled paradigm that allows usual manipulations of attentional load (e.g., ITI variability; stimulus characteristics) as well as new protocols to quantify other aspects of attention (e.g., sustained) in rats.