A Simple Behavioral Paradigm to Measure Impulsive Behavior in an Animal Model of Attention Deficit Hyperactivity Disorder (ADHD) of the Spontaneously Hypertensive Rats = A Simple Behavioral Paradigm to Measure Impulsive Behavior in an Animal Model of Attention Deficit Hyperactivity Disorder (ADHD) of the Spontaneously Hypertensive Rats

다국어 초록 (Multilingual Abstract)

Impulsiveness is an important component of many psychiatric disorders including Attention-deficit/hyperactivity disorder (ADHD). Although the neurobiological basis of ADHD is unresolved, behavioral tests in animal models have become indispensable tools for improving our understanding of this disorder. In the punishment/extinction paradigm, impulsivity is shown by subjects that persevere with responding despite punishment or unrewarded responses. Exploiting this principle, we developed a new behavioral test that would evaluate impulsivity in the most validated animal model of ADHD of the Spontaneously Hypertensive rat (SHR) as compared with the normotensive control strain, the Wistar Kyoto rat (WKY). In this paradigm we call the Electro-Foot Shock aversive water Drinking test (EFSDT), water-deprived rats should pass over an electrified quadrant of the EFSDT apparatus to drink water. We reasoned that impulsive animals show increased frequency to drink water even with the presentation of an aversive consequence (electro-shock). Through this assay, we showed that the SHR was more impulsive than the WKY as it demonstrated more drinking attempts and drinking frequency. Methylphenidate, the most widely used ADHD medication, significantly reduced drinking frequency of both SHR and WKY in the EFSDT. Thus, the present assay may be considered as another behavioral tool to measure impulsivity in animal disease models, especially in the context of ADHD.

참고문헌 (Reference)

1 Evenden, J. L., "Varieties of impulsivity" 146 : 348-361, 1999

2 Wultz, B., "The spontaneously hypertensive rat as an animal model of attentiondefi cit hyperactivity disorder: effects of methylphenidate on exploratory behavior" 53 : 88-102, 1990

3 Eysenck, S. B. G., "The I7: development of a measure of impulsivity and its relationship to the superfactors of personality. In The Impulsive Client: Theory, Research, and Treatment" American Psychological Association 141-149, 1993

4 Robbins, T. W., "The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry" 163 : 362-380, 2002

5 van den Bergh, F. S., "Spontaneously hypertensive rats do not predict symptoms of attention-defi cit hyperactivity disorder" 83 : 380-390, 2006

6 Berger, D. F., "Sex differences in operant discrimination behaviour in an animal model of attention-defi cit hyperactivity disorder" 94 : 73-82, 1998

7 Mill, J., "Sequence analysis of Drd2, Drd4, and Dat1 in SHR and WKY rat strains" 1 : 24-, 2005

8 Nigg, J. T., "Response inhibition and disruptive behaviors: toward a multiprocess conception of etiological heterogeneity for ADHD combined type and conduct disorder early-onset type" 1008 : 170-182, 2003

9 Sonuga-Barke, E. J., "Psychological heterogeneity in AD/HD--a dual pathway model of behaviour and cognition" 130 : 29-36, 2002

10 Moeller, F. G., "Psychiatric aspects of impulsivity" 158 : 1783-1793, 2001

11 Alsop, B., "Problems with spontaneously hypertensive rats (SHR) as a model of attention-defi cit/hyperactivity disorder (AD/ HD)" 162 : 42-48, 2007

12 Bizot, J. C., "Methylphenidate reduces impulsive behaviour in juvenile Wistar rats, but not in adult Wistar, SHR and WKY rats" 193 : 215-223, 2007

13 Dougherty, D. M., "Laboratory behavioral measures of impulsivity" 37 : 82-90, 2005

14 Barratt, E., "Impulsiveness and aggression. In Violence and Mental Disorder: Developments in Risk Assessment" University of Chicago Press 61-80, 1994

15 Fox, A. T., "Impulsive choice in a rodent model of attention-defi cit/hyperactivity disorder" 187 : 146-152, 2008

16 Jensen PS, "Epidemiological Research on ADHD: What We Know and What We Need to Learn" ADHD

17 Mook, D. M., "Different effects of amphetamine on reinforced variations versus repetitions in spontaneously hypertensive rats (SHR)" 56 : 939-944, 1994

18 American Psychiatric Association, "Diagnostic criteria from DSM-IV-TR" American Psychiatric Association 2000

19 De Bruin, N. M., "Combined uridine and choline administration improves cognitive defi cits in spontaneously hypertensive rats" 80 : 63-79, 2003

20 Harrison, A. A., "Central serotonin depletion impairs both the acquisition and performance of a symmetrically reinforced go/no-go conditional visual discrimination" 100 : 99-112, 1999

21 Sagvolden, T., "Behavioral validation of the spontaneously hypertensive rat (SHR) as an animal model of attention-defi cit/hyperactivity disorder (AD/HD)" 24 : 31-39, 2000

22 Sarter, M., "Behavioral screening for cognition enhancers: from indiscriminate to valid testing: Part I" 107 : 144-159, 1992

23 Hard, E., "Behavioral reactivity in spontaneously hypertensive rats" 35 : 487-492, 1985

24 Winstanley, C. A., "Behavioral models of impulsivity in relation to ADHD: translation between clinical and preclinical studies" 26 : 379-395, 2006

25 McKinney, W. T. Jr., "Animal model of depression. I. Review of evidence: implications for research" 21 : 240-248, 1969

26 Sagvolden, T., "Altered reinforcement mechanisms in attention-defi cit/hyperactivity disorder" 94 : 61-71, 1998

27 Hendley, E. D., "Age, sex and strain differences in activity and habituation in SHR and WKY rats" 34 : 379-383, 1985

28 Cloninger, C. R., "A systematic method for clinical description and classifi cation of personality variants" 44 : 573-588, 1987

29 Daruna, J. H, "A neurodcvelopmental view of impulsivity. In The Impulsive Client: Theory, Research and Treatment" American Psychological Association 76-89, 1993