The spontaneously hypertensive-rat as an animal model of ADHD: evidence for impulsive and non-impulsive subpopulations

Adriani, Walter; Caprioli, Antonio; Granstrem, Oleg; Carli, Mirjana; Laviola, Giovanni

doi:10.1016/j.neubiorev.2003.08.007

Cited by 163 publications

(134 citation statements)

References 74 publications

Supporting

Mentioning

119

Contrasting

Order By: Relevance

“…Noteworthy, this robust finding was obtained without the need of splitting the groups into halves, i.e. the most and least impulsive subgroups (see Adriani et al, 2003). Without such splitting, all the variability due to the presence of individual differences is loaded to the residual error, instead of the sub-population factor, and the ANOVA is hence much more conservative.…”

Section: Experiments 2: Delay-intolerance Task For Impulsivitymentioning

confidence: 89%

Increased impulsive behavior and risk proneness following lentivirus-mediated dopamine transporter over-expression in rats' nucleus accumbens

et al. 2009

View full text Add to dashboard Cite

Abstract-Multiple theories have been proposed for sensation seeking and vulnerability to impulse-control disorders [Zuckerman M, Kuhlman DM (2000) Personality and risk-taking: Common biosocial factors. J Pers 68:999 -1029], and many of these rely on a dopamine system deficit. Available animal models reproduce only some behavioral symptoms and seem devoid of construct validity. We used lentivirus tools for over-expressing or silencing the dopamine transporter (DAT) and we evaluated the resulting behavioral profiles in terms of motivation and self-control. Wistar adult rats received stereotaxic inoculation of a lentivirus that allowed localized intra-accumbens delivery of a DAT gene enhancer/ silencer, or the green fluorescent protein, GFP. These animals were studied for intolerance to delay, risk proneness and novelty seeking. As expected, controls shifted their demanding from a large reward toward a small one when the delivery of the former was increasingly delayed (or uncertain). Interestingly, in the absence of general locomotor effects, DAT over-expressing rats showed increased impulsivity (i.e. a more marked shift of demanding from the large/ delayed toward the small/soon reward), and increased risk proneness (i.e. a less marked shift from the large/uncertain toward the small/sure reward), compared with controls. Rats with enhanced or silenced DAT expression did not show any significant preference for a novel environment. In summary, consistent with literature on comorbidity between attentiondeficit/hyperactivity disorder and pathological gambling, we demonstrate that DAT over-expression in rats' nucleus accumbens leads to impulsive and risk prone phenotype. Thus, a reduced dopaminergic tone following altered accumbal DAT function may subserve a sensation-seeker phenotype and the vulnerability to impulse-control disorders.

show abstract

Section: Experiments 2: Delay-intolerance Task For Impulsivitymentioning

confidence: 89%

Increased impulsive behavior and risk proneness following lentivirus-mediated dopamine transporter over-expression in rats' nucleus accumbens

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Notwithstanding the fact that most of SH rats belong to attentively-low phenotype, the population includes 19% of attentively-high rats. The heterogeneity could at least partially account for high variability of the ADHD-like behavior having been reported in SH rats [14,19,23] and the ED-test might be useful for obtaining of more robust results in the tests for exploratory behavior and attention.…”

Section: Discussionmentioning

confidence: 99%

“…The ADHD-like pattern in SH rats, however, is not related to blood pressure level [15]. In SH rat, learning may be either enhanced or constrained across different tests [16][17][18] because the SH individuals are more impulsive [8,19,20] and less anxious [21,22] than normotensive animals. Some criticism comes from the fact that, in instrumental paradigms, variability in general activity also contribute to ADHDlike pattern typical for SH rats [23] suggesting the necessity of development of procedures that independently measure attention, cognitive performance and general activity in experimental animal.…”

Section: Introductionmentioning

confidence: 95%

“…Recently it has been found that the SH rat strain is not homogeneous with regard to delayed instrumental responding [14] and include subpopulations of, so-called, impulsive and non-impulsive individuals [19] albeit the result is not illustrated by analysis of frequency distribution and its clinical relevance is not fully supported by effects of drugs [20]. Non-homogeneity of SH strain in measures of attentional behavior per se has never been studied before.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Enrichment Discrimination Behavior in Spontaneously Hypertensive Rats

Salimov¹,

Ковалев²

2012

JBBS

View full text Add to dashboard Cite

Objectives: 1) To reveal, among spontaneously hypertensive rats, subpopulations that diverge in attention to objects enriching an empty cross-maze; 2) To evaluate effect of clinically efficient drug for treatment of attention deficiency atomoxetine on the attention to environmental cues in attentionally-low rats. Method: A novel paradigm that provides measure of attention towards enriching objects independent of general locomotor activity and spatial orientation is employed. The apparatus consists of 4-arm radial maze, two arms of which contain objects (enriched compartments). Animals exploring the objects typically stay longer in enriched parts of maze than in empty arms and have a higher score of enrichment discrimination ratio. Results: Frequency distribution of the enrichment discrimination ratio had clear bimodal shape that differed significantly from normal distribution suggesting the existence of subpopulations of attentionally-low and -high individuals. The attentionally-low phenotype did not show inferiority in spatial orientation as compared with attentionally-high phenotype. The phenotypes did not differ from each other in measures of locomotor activity and blood pressure. Atomoxetine (3 mg/kg, orally, once daily for 4 days) enhanced enrichment discrimination in animals of attentionally-low phenotype. Single administration of the drug was ineffective. Conclusion: Population of spontaneously hypertensive rat includes two phenotypes of attentionally-low and -high individuals. Subchronic atomoxetine ameliorates attention to environmental cues in attentionally-low rats. The enrichment discrimination test could be useful in studies of neurobiology of attention deficit condition and for screening of novel drug candidates.

show abstract

“…Rats were continuously monitored for spontaneous home-cage locomotor activity [3,4] by means of an automatic device equipped with small passive infrared sensors placed on a standard rack over the top of each home-cage (ActiviScope system; TechnoSmart, Rome, Italy). These sensors (20 Hz) detected any movement of rats: scores were automatically divided into 60-min intervals.…”

Section: Circadian Cyclementioning

confidence: 99%

Impulsivity and home-cage activity are decreased by lentivirus-mediated silencing of serotonin transporter in the rat hippocampus

Zoratto

Tringle

Bellenchi

et al. 2013

Neuroscience Letters

Self Cite

View full text Add to dashboard Cite

h i g h l i g h t s• Lenti-SERT vectors were designed to suppress SERT gene expression in vivo.• We evaluated a rat model of ADHD through hippocampal inoculation of Lenti-SERT.• Lenti-SERT rats exhibited less pronounced peaks of circadian activity than controls.• Lenti-SERT rats displayed a transient decrease in cognitive impulsivity.• Such phenotype is consistent both with 5-HT manipulations and hippocampal lesions.Brain serotonin (5-HT) systems modulate emotional, motivational and cognitive processes. Mutations in the serotonin transporter (SERT) gene have been associated with susceptibility towards the development of several psychiatric disorders, both in humans and animal models. Present approach exploited a bilateral intra-hippocampus stereotaxic inoculation of lentiviruses, for enduring in vivo silencing of SERT. Control rats were bilaterally inoculated with heat-inactivated lentiviruses. These Lenti-SERT vectors were intended to eventually manipulate the neurotransmitter reuptake at synaptic level, thus enhancing tonic 5-HT transmission. We investigated whether such manipulation could induce behavioural alterations relevant to the modelling of ADHD, in particular symptoms of hyperactivity and impulsivity. Wistar rats were monitored for spontaneous home-cage locomotor activity and studied for impulsivity (Intoleranceto-Delay task). Results show that rats inoculated with Lenti-SERT vectors exhibited less pronounced circadian peaks of activity than controls. Moreover, Lenti-SERT compared to control rats exhibited a transient increase in choice for a delayed-larger reward over an immediate-small reward. This suggests that enhanced hippocampal serotonergic transmission produced a profile of restfulness and a decrease in cognitive impulsivity. This phenotype is consistent with available data both on 5-HT manipulations and hippocampal lesions. In conclusion, present findings may possibly disclose novel avenues towards the development of innovative therapeutical approaches for behavioural symptoms relevant to ADHD.

show abstract

The spontaneously hypertensive-rat as an animal model of ADHD: evidence for impulsive and non-impulsive subpopulations

Cited by 163 publications

References 74 publications

Increased impulsive behavior and risk proneness following lentivirus-mediated dopamine transporter over-expression in rats' nucleus accumbens

Increased impulsive behavior and risk proneness following lentivirus-mediated dopamine transporter over-expression in rats' nucleus accumbens

Enrichment Discrimination Behavior in Spontaneously Hypertensive Rats

Impulsivity and home-cage activity are decreased by lentivirus-mediated silencing of serotonin transporter in the rat hippocampus

Contact Info

Product

Resources

About