Common genetic effects on variation in impulsivity and activity in mice

被引:85
作者
Isles, AR
Humby, T
Walters, E
Wilkinson, LS [1 ]
机构
[1] Babraham Inst, Neurobiol Programme, Cambridge CB2 4AT, England
[2] Babraham Inst, Dev Genet Programme, Cambridge CB2 4AT, England
关键词
impulsivity; activity; heritability; delayed reinforcement; mice; AD/HD;
D O I
10.1523/JNEUROSCI.1650-04.2004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Impulsivity is a complex psychological construct that impacts on behavioral predispositions in the normal range and has been shown to have a genetic element through the examination of hereditary patterns of abnormal conditions such as attention deficit/hyperactivity disorder and obsessive compulsive disorder. In this study, we took advantage of the isogenic nature of inbred strains of mice to determine the contribution of genes to impulsive behaviors by examining the performance of four separate mouse strains in a novel murine delayed-reinforcement paradigm, during which the animals had to choose between rewards that were relatively small but available immediately and larger but progressively delayed rewards. To control for maternal effects, all the mice were cross-fostered to a common strain immediately after birth. Under these conditions, we found significant differences between the strains on behaviors indexing impulsive choice and on independent measures of locomotor activity, which subsequent heritability analysis showed could be related, in part, to genetic effects. Moreover, the two aspects of behavior were found to co-vary, with the more active animals also displaying more impulsive behavior. This was not attributable to mundane confounds related to individual task requirements but instead indicated the existence of common genetic factors influencing variation in both impulsivity and locomotor activity. The data are discussed in terms of the coexistence of impulsivity and hyperactivity, interactions between environmental and genetic effects, and possible candidate genes.
引用
收藏
页码:6733 / 6740
页数:8
相关论文
共 48 条
[1]   DOPAMINE D2 RECEPTOR GENE VARIANTS - ASSOCIATION AND LINKAGE STUDIES IN IMPULSIVE-ADDICTIVE-COMPULSIVE BEHAVIOR [J].
BLUM, K ;
SHERIDAN, PJ ;
WOOD, RC ;
BRAVERMAN, ER ;
CHEN, TJH ;
COMINGS, DE .
PHARMACOGENETICS, 1995, 5 (03) :121-141
[2]   Absence of 5-HT1B receptors is associated with impaired impulse control in male 5-HT1B knockout mice [J].
Bouwknecht, JA ;
Hijzen, TH ;
van der Gugten, J ;
Mass, RAA ;
Hen, R ;
Olivier, B .
BIOLOGICAL PSYCHIATRY, 2001, 49 (07) :557-568
[3]   Insights into the neurobiology of impulsive behavior from serotonin receptor knockout mice [J].
Brunner, D ;
Hen, R .
NEUROBIOLOGY OF SUICIDE: FROM THE BENCH TO THE CLINIC, 1997, 836 :81-105
[4]   ABNORMAL-BEHAVIOR ASSOCIATED WITH A POINT MUTATION IN THE STRUCTURAL GENE FOR MONOAMINE OXIDASE-A [J].
BRUNNER, HG ;
NELEN, M ;
BREAKEFIELD, XO ;
ROPERS, HH ;
VANOOST, BA .
SCIENCE, 1993, 262 (5133) :578-580
[5]  
BRUNNER HG, 1993, AM J HUM GENET, V52, P1032
[6]   The effects of d-amphetamine, chlordiazepoxide, α-flupenthixol and behavioural manipulations on choice of signalled and unsignalled delayed reinforcement in rats [J].
Cardinal, RN ;
Robbins, TW ;
Everitt, BJ .
PSYCHOPHARMACOLOGY, 2000, 152 (04) :362-375
[7]   Impulsive choice induced in rats by lesions of the nucleus accumbens core [J].
Cardinal, RN ;
Pennicott, DR ;
Sugathapala, CL ;
Robbins, TW ;
Everitt, BJ .
SCIENCE, 2001, 292 (5526) :2499-2501
[8]   Role of genotype in the cycle of violence in maltreated children [J].
Caspi, A ;
McClay, J ;
Moffitt, TE ;
Mill, J ;
Martin, J ;
Craig, IW ;
Taylor, A ;
Poulton, R .
SCIENCE, 2002, 297 (5582) :851-854
[9]   Population migration and the variation of dopamine D4 receptor (DRD4) allele frequencies around the globe [J].
Chen, CS ;
Burton, M ;
Greenberger, E ;
Dmitrieva, J .
EVOLUTION AND HUMAN BEHAVIOR, 1999, 20 (05) :309-324
[10]   Decision-making deficits in drug addiction [J].
Clark, L ;
Robbins, TW .
TRENDS IN COGNITIVE SCIENCES, 2002, 6 (09) :361-363