Abstract
Rationale
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.
Objectives
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.
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References
Bickel WK, Odum AL, Madden GJ (1999) Impulsivity and cigarette smoking: delay discounting in current, never, and ex-smokers. Psychopharmacology 146:447–454
Bouwknecht JA, Hijzen TH, van der Gugten J, Maes RA, Hen R, Olivier B (2001) Absence of 5-HT(1B) receptors is associated with impaired impulse control in male 5-HT(1B) knockout mice. Biol Psychiatry 49:557–568
Brunner D, Hen R (1997) Insights into the neurobiology of impulsive behavior from serotonin receptor knockout mice. Ann NY Acad Sci 836:81–105
Cardinal RN, Robbins TW, Everitt BJ (2000) The effects of d-amphetamine, chlordiazepoxide, alpha-flupenthixol and behavioural manipulations on choice of signalled and unsignalled delayed reinforcement in rats. Psychopharmacology 152:362–375
Cardinal RN, Pennicott DR, Sugathapala CL, Robbins TW, Everitt BJ (2001) Impulsive choice induced in rats by lesions of the nucleus accumbens core. Science 292:2499–2501
Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R (2002) Role of genotype in the cycle of violence in maltreated children. Science 297:851–854
Clark L, Robbins T (2002) Decision-making deficits in drug addiction. Trends Cognit Sci 6:361
Cochran W, Cox G (1957) Experimental designs, 2nd edn. Wiley, New York
de Wit H, Crean J, Richards JB (2000) Effects of d-amphetamine and ethanol on a measure of behavioral inhibition in humans. Behav Neurosci 114:830–837
Evenden J (1999a) Impulsivity: a discussion of clinical and experimental findings. J Psychopharmacol 13:180–192
Evenden JL (1999b) Varieties of impulsivity. Psychopharmacology 146:348–361
Evenden J, Meyerson B (1999) The behavior of spontaneously hypertensive and Wistar Kyoto rats under a paced fixed consecutive number schedule of reinforcement. Pharmacol Biochem Behav 63:71–82
Evenden JL, Ryan CN (1996) The pharmacology of impulsive behaviour in rats: the effects of drugs on response choice with varying delays of reinforcement. Psychopharmacology 128:161–170
Hen R (1996) Mean genes. Neuron 16:17–21
Ho MY, Mobini S, Chiang TJ, Bradshaw CM, Szabadi E (1999) Theory and method in the quantitative analysis of "impulsive choice" behaviour: implications for psychopharmacology. Psychopharmacology 146:362–372
Humby T, Laird FM, Davies W, Wilkinson LS (1999) Visuospatial attentional functioning in mice: interactions between cholinergic manipulations and genotype. Eur J Neurosci 11:2813–2823
Kirby KN, Petry NM, Bickel WK (1999) Heroin addicts have higher discount rates for delayed rewards than non-drug-using controls. J Exp Psychol Gen 128:78–87
Mazur JE (2000) Tradeoffs among delay, rate, and amount of reinforcement. Behav Proc 49:1–10
McGue M, Bouchard TJ Jr (1998) Genetic and environmental influences on human behavioral differences. Annu Rev Neurosci 21:1–24
Mobini S, Chiang TJ, Ho MY, Bradshaw CM, Szabadi E (2000) Effects of central 5-hydroxytryptamine depletion on sensitivity to delayed and probabilistic reinforcement. Psychopharmacology 152:390–397
Mobini S, Body S, Ho MY, Bradshaw CM, Szabadi E, Deakin JF, Anderson IM (2002) Effects of lesions of the orbitofrontal cortex on sensitivity to delayed and probabilistic reinforcement. Psychopharmacology 160:290–298
Nelson RJ, Demas GE, Huang PL, Fishman MC, Dawson VL, Dawson TM, Snyder SH (1995) Behavioural abnormalities in male mice lacking neuronal nitric oxide synthase. Nature 378:383–386
Petry NM (2001) Pathological gamblers, with and without substance use disorders, discount delayed rewards at high rates. J Abnorm Psychol 110:482–487
Rachlin H, Raineri A, Cross D (1991) Subjective probability and delay. J Exp Anal Behav 55:233–244
Rapoport JL, Buchsbaum MS, Zahn TP, Weingartner H, Ludlow C, Mikkelsen EJ (1978) Dextroamphetamine: cognitive and behavioral effects in normal prepubertal boys. Science 199:560–563
Richards JB, Sabol KE, de Wit H (1999) Effects of methamphetamine on the adjusting amount procedure, a model of impulsive behavior in rats. Psychopharmacology 146:432–439
Sagvolden T, Metzger MA, Schiorbeck HK, Rugland AL, Spinnangr I, Sagvolden G (1992) The spontaneously hypertensive rat (SHR) as an animal model of childhood hyperactivity (ADHD): changed reactivity to reinforcers and to psychomotor stimulants. Behav Neural Biol 58:103–112
Sarter M, Berntson GG (1999) Tapping artificially into natural talents. Trends Neurosci 22:300–302
Sheppard DM, Bradshaw JL, Purcell R, Pantelis C (1999) Tourette's and comorbid syndromes: obsessive compulsive and attention deficit hyperactivity disorder. A common etiology? Clin Psychol Rev 19:531–552
Solanto MV (1998) Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration. Behav Brain Res 94:127–152
Sonuga-Barke EJ, Taylor E, Sembi S, Smith J (1992) Hyperactivity and delay aversion—I. The effect of delay on choice. J Child Psychol Psychiatry 33:387–398
Swanson J, Posner M, Fusella J, Wasdell M, Sommer T, Fan J (2001) Genes and attention deficit hyperactivity disorder. Curr Psychiatry Rep 3:92–100
Wade TR, de Wit H, Richards JB (2000) Effects of dopaminergic drugs on delayed reward as a measure of impulsive behavior in rats. Psychopharmacology 150:90–101
Acknowledgements
This work was supported by the BBSRC. T. Humby was in receipt of a research studentship from Cambridge Cognition Ltd and the Oon Khye Beng Ch-hia Tsio prize studentship from Downing College, Cambridge.
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Isles, A.R., Humby, T. & Wilkinson, L.S. Measuring impulsivity in mice using a novel operant delayed reinforcement task: effects of behavioural manipulations and d-amphetamine. Psychopharmacology 170, 376–382 (2003). https://doi.org/10.1007/s00213-003-1551-6
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DOI: https://doi.org/10.1007/s00213-003-1551-6