Impulsivity is a heritable trait in rodents and associated with a novel quantitative trait locus on chromosome 1.

Impulsivity describes the tendency to act prematurely without appropriate foresight and is symptomatic of a number of neuropsychiatric disorders. Although a number of genes for impulsivity have been identified, no study to date has carried out an unbiased, genome-wide approach to identify genetic markers associated with impulsivity in experimental animals. Herein we report a linkage study of a six-generational pedigree of adult rats phenotyped for one dimension of impulsivity, namely premature responding on the five-choice serial reaction time task, combined with genome wide sequencing and transcriptome analysis to identify candidate genes associated with the expression of the impulsivity trait. Premature responding was found to be heritable (h2 = 13-16%), with significant linkage (LOD 5.2) identified on chromosome 1. Fine mapping of this locus identified a number of polymorphic candidate genes, however only one, beta haemoglobin, was differentially expressed in both the founder strain and F6 generation. These findings provide novel insights into the genetic substrates and putative neurobiological mechanisms of impulsivity with broader translational relevance for impulsivity-related disorders in humans.

Ethanol effects on impulsivity in two mouse strains: similarities to diazepam and ketamine.

RATIONALE: The effects of ethanol on attention and impulsivity have been contradictory. OBJECTIVES: The aim of the present investigation is to study the effects of acute ethanol administration in measures of attention and response control in the five-choice serial reaction time task (5-CSRTT) in two strains of mice, C57BL/6JOlaHsd and CD1. MATERIALS AND METHODS: Mice were trained in the 5-CSRTT and then were injected intraperitoneally (i.p.) with 0, 0.5, 1 and 2 g/kg ethanol before testing under standard parameters and in a long inter-trial interval (ITI) session, which promotes the emergence of premature responses, a measure of poor inhibitory control. To examine if the effects of ethanol in the 5-CSRTT were due to its actions at GABA(A) receptors or at NMDA receptors, the GABA(A) receptor agonist diazepam (1 and 2 mg/kg, i.p.) and the non-competitive NMDA antagonist ketamine (10 and 20 mg/kg, i.p.) were tested in long ITI sessions. RESULTS: Ethanol did not affect attention or impulsivity in the standard procedure, but increased premature responding in long ITI sessions. The effects of ethanol were mimicked by diazepam in both strains of mice, whereas ketamine increased premature responding only in the CD1 strain. CONCLUSIONS: Ethanol's ability to increase impulsivity in the 5-CSRTT is mediated by both common and different neurotransmitter systems in the two strains of mice and is dependent on the task's parameters. Furthermore, ethanol did not decrease response accuracy, suggesting that attentional mechanisms are preserved after acute ethanol in mice and that the increases in impulsive behaviour are independent of attentional performance.