Measuring impulsivity in mice using a novel operant delayed reinforcement task: effects of behavioural manipulations and d-amphetamine.
BACKGROUND
The increasing use of genetically modified mice to probe genetic contributions to normal and abnormal behaviours requires the development of sensitive and selective behavioural tasks.


OBJECTIVE
To develop a discrete trial assay of impulsivity (delayed reinforcement) that is tractable in mice utilising a mouse operant nine-hole box apparatus and to specify the task with respect to behavioural and pharmacological manipulations.


METHODS
Mice were trained to respond with a nose-poke to one of two visual stimuli; one response resulted in a small quantity of reinforcer, the other in a larger quantity of reinforcer. As the session proceeded increasing delay was introduced onto the response leading to the large reward. Hence, the nature of the choice was a small quantity of reinforcer immediately versus a larger but progressively delayed amount of reinforcer. At stable baseline performance the mice were challenged with a variety of task manipulations and systemic d-amphetamine in order to discern aspects of the underlying psychological and neurochemical substrates of the choice behaviour.


RESULTS
The mice showed a systematic shift in responding away from the large reinforcer with increasing delay (0, 2, 4, 8, 12 s), such that at the longest delay >80% of nose-pokes were for the smaller, immediate reinforcer. Task manipulations indicated that behaviour was controlled in a trial discrete manner by the contingency between delay and reward and was not due to non-specific factors such as satiation. d-Amphetamine had complex, dose dependent effects on choice behaviour which revealed dissociations between impulsive choice and hyperactivity.


CONCLUSIONS
We have successfully developed an assay of impulsivity in mice that will be of utility to examine impulsive behaviours and their genetic substrates. In addition, our data provided evidence of distinct dopaminergic mechanisms mediating aspects of impulsivity and hyperactivity.
Isles
Anthony R
AR
Laboratory of Cognitive and Behavioural Neuroscience, Neurobiology Programme, The Babraham Institute, Babraham, Cambridge CB2 4AT, UK.
Humby
Trevor
T
Wilkinson
Lawrence S
LS
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D007175:Impulsive Behavior / Q000235:genetics*; D008297:Male; D051379:Mice; D013997:Time Factors
D000697:Central Nervous System Stimulants; D000661:Amphetamine